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Therapeutic Agents as Potential Carcinogens

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Chemical Carcinogenesis and Mutagenesis I

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 94 / 1))

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Abstract

In spite of the antiquity of medicine as a profession, an appreciation of the fact that therapeutic agents can cause cancer is relatively recent. Interestingly enough, much of this understanding evolved concurrently with the development of cancer chemotherapy. The use of nitrogen mustard for the treatment of malignancies began in the 1940s, and various congeners of this compound were synthesised and introduced into practice shortly thereafter (Calabresi and Parks 1985). One of these, chlornaphazine, proved to be a bladder carcinogen (Thiede and Christiensen 1969). Subsequently, concerns have arisen that other therapeutic agents, including those used in general practice, might also cause malignancies.

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References

  • Arseneau JC, Canellos GP, Johnson R, DeVita VT (1977) Risk of new cancers in patients with Hodgkin’s disease. Cancer 40: 1912–1916.

    Article  PubMed  CAS  Google Scholar 

  • Auclerc G, Jacquillat C, Auclerc MF, Weil M, Bernard J (1979) Post-therapeutic acute leukaemia. Cancer 44: 2017–2025.

    Article  PubMed  CAS  Google Scholar 

  • Aymard JP, Frustin J, Witz F, Columb JN, Lederlin P, Herbeuval R (1980) Acute leukaemia after prolonged chlorambucil treatment for non-malignant disease: report of a new case and literature survey. Acta Haematol 63: 283–285.

    Article  PubMed  CAS  Google Scholar 

  • Bacci M, Cavaliere A, Fratini D (1982) Lung carcinogenesis by procarbazine chlorate in BALB/c mice. Carcinogenesis 3: 71–73.

    Article  PubMed  CAS  Google Scholar 

  • Bacci M, Cavaliere A, Amorosi A (1984) Procarbazine hydrochlorate carcinogenesis in Osborne-Mendel rats. Oncology 41: 106–108.

    Article  PubMed  CAS  Google Scholar 

  • Beal DD, Skibba JL, Croft WA, Cohen SM, Bryan GT (1975) Carcinogenicity of the antineoplastic agent, 5-(3,3-dimethyl-l-triazeno)-imidazole-4-carboxamide, and its metabolites in rats. JNCI 54: 951–957.

    Google Scholar 

  • Bennett RA, Pegg AE (1981) Alkylation of DNA in rat tissues following administration of streptozotocin. Cancer Res 41–2786–2790.

    Google Scholar 

  • Berk PD, Goldberg JD, Silverstein MN, Weinfeld A, Donovan PB, Ellis JT, Landaw SA, Laszlo J, Najean Y, Pisciotta AV, Wasserman LR (1981) Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med 304: 441–447.

    Article  PubMed  CAS  Google Scholar 

  • Blanc AP, Gastaut JA, Sebahoun G, Dalivoust P, Murisasco A, Carcassone Y (1981) Naissance d’une leucémie aiguë au décours d’un traitement immunosuppresseur par le chlorambucil: une observation. Nouv Presse Med 10: 1717–1719.

    PubMed  CAS  Google Scholar 

  • Boice JD Jr, Greene MH, Killen JY Jr, Ellenberg SS, Keehn RJ, McFadden E, Chen TT, Fraumeni JF Jr (1983) Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU). N Engl J Med 309: 1079–1084.

    Article  PubMed  Google Scholar 

  • Boice JD Jr, Greene MH, Killen J Y Jr, Ellenberg SS, Fraumeni JF Jr (1986) Leukemia after adjuvant chemotherapy with semustine (methyl-CCNU). Evidence of a dose- response effect. N Engl J Med 314: 119–120.

    Google Scholar 

  • Brock N, Hohorst H-J (1963) Ãœber die Aktivierung von Cyclophosphamid in vivo und in vitro. Arzneimittelforsch 1021: 1–31.

    Google Scholar 

  • Calabresi P, Parks RE Jr (1985) Chemotherapy of neoplastic diseases. In: Gilman AG, Goodman LS, Rail TW, Murad F (eds) Goodman and Gilman’s The pharmacological basis of therapeutics, 7th edn. MacMillan, New York, pp 1240–1306.

    Google Scholar 

  • Calder IC, Goss DE, Wilhams PJ, Funder CC, Green CR, Ham KN, Tange JD (1976) Neoplasia in the rat induced by IV-hydroxyphenacetin, a metabolite of phenacetin. Pathology 8: 1–6.

    Article  PubMed  CAS  Google Scholar 

  • Cavaliere A, Bacci M, Amorosi A, Del Gaudio M, Vitali R (1983) Induction of lung tumors and lymphomas in BALB/c mice by metronidazole. Tumori 69: 379–382.

    PubMed  CAS  Google Scholar 

  • Cavaliere A, Bacci M, Vitali R (1984) Induction of mammary tumors with metronidazole in female Sprague-Dawley rats. Tumori 70: 307–311.

    PubMed  CAS  Google Scholar 

  • Chetsanga CJ, Polidori G, Mainwaring M (1982) Analysis and excision of ring-opened phosphoramide mustard-deoxyguanosine adducts in DNA. Cancer Res 42: 2616–2621.

    PubMed  CAS  Google Scholar 

  • Chrystal JT, Koch RL, Goldman P (1980) Metabolites from the reduction of metronidazole by xanthine oxidase. Mol Pharmacol 18: 105–111.

    PubMed  CAS  Google Scholar 

  • Cohen SM, Ertiirk E, Van Esch AM, Crovetti AJ, Bryan GT (1973) Carcinogenicity of 5- nitrofurans, 5-nitroimidazoles, 4-nitrobenzenes, and related compounds. JNCl 51: 403–417.

    Google Scholar 

  • Coltman CA, Dixon DO (1982) Second malignancies complicating Hodgkin’s disease: a Southwest Oncology Group 10-year followup. Cancer Treat Rep 66: 1023–1033.

    PubMed  Google Scholar 

  • Colvin M, Padgett CA, Fenselau C (1973) A biologically active metabolite of cyclophosphamide. Cancer Res 33: 915–918.

    PubMed  CAS  Google Scholar 

  • Colvin M, Brundrett RB, Kan M-NN, Jardine I, Fenselau C (1976) Alkylating properties of phosphoramide mustard. Cancer Res 36: 1121–1126.

    PubMed  CAS  Google Scholar 

  • Connors TA (1984) Carcinogenicity of medicines. In: Searle CE (ed) Chemical carcinogens, 2nd edn, vol II. ACS Monograph 182, Washington DC, pp 1241–1278.

    Google Scholar 

  • Connors TA, Cox PJ, Farmer PB, Foster AB, Jarman M (1974) Some studies of the active intermediates formed in the microsomal metabolism of cyclophosphamide and isophosphamide. Biochem Pharmacol 23: 115–129.

    Article  PubMed  CAS  Google Scholar 

  • Demple B, Sedgwick B, Robins P, Totty N, Waterfield MD, Lindahl T (1985) Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis. Proc Natl Acad Sci USA 82: 2688–2692.

    Article  PubMed  CAS  Google Scholar 

  • Doll R, Peto R (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. JNCI66: 1191–1308.

    Google Scholar 

  • Dumont J, Thiery JP, Mazabraud A, Natali JC, Trapet P, Vilcoq JR (1980) Acute myeloid leukemia following non-Hodgkin’s lymphoma: danger of prolonged use of chlorambucil as maintenance therapy. Nouv Rev Fr Hematol 22: 391–404.

    PubMed  CAS  Google Scholar 

  • Einhorn N (1978) Acute leukemia after chemotherapy (melphalan). Cancer 41: 444–447.

    Article  PubMed  CAS  Google Scholar 

  • Fries JF, Bloch D, Spitz P, Mitchell DM (1985) Cancer in rheumatoid arthritis: a prospective long-term study of mortality. Am J Med (Suppl 1 A) 78: 56–59.

    CAS  Google Scholar 

  • Gardner WU (1941) The effect of estrogen on the incidence of mammary and pituitary tumors in hybrid mice. Cancer Res 1: 345–358.

    CAS  Google Scholar 

  • Gerard SS, Gardner B, Patti J, Husain V, Shouten J, Alfonso AE (1980) Effects of triiodothyronine and reserpine on induction and growth of mammary tumors in rats by 3-methylcholanthrene. J Surg Oncol 14: 213–218.

    Article  PubMed  CAS  Google Scholar 

  • Glicksman AS, Pajak TF, Gottlieb A, Nissen N, Stutzman L, Cooper MR (1982) Second malignant neoplasms in patients successfully treated for Hodgkin’s disease: a Cancer and Leukemia Group B study. Cancer Treat Rep 66: 1035–1044.

    PubMed  CAS  Google Scholar 

  • Glucksmann A, Cherry CP (1968) The effect of oestrogens, testosterone and progesterone on the induction of cervico-vaginal tumours in intact and castrate rats. Br J Cancer 22: 545–562.

    Article  PubMed  CAS  Google Scholar 

  • Gombar CT, Tong WP, Ludlum DB (1980) Mechanism of action of the nitroso-ureas IV: reactions of BCNU and CCNU with DNA. Biochem Pharmacol 29: 2639–2643.

    Article  PubMed  CAS  Google Scholar 

  • Greene MH, Boice JD Jr, Strike TA (1985) Carmustine as a cause of acute nonlymphocytic leukemia. N Engl J Med 313: 579.

    Article  PubMed  CAS  Google Scholar 

  • Habs M, Schmâhl D (1984) Long-term toxic and carcinogenic effects of cytostatic drugs. Dev Oncol 15: 201–209.

    Google Scholar 

  • Harousseau JL, Andrieu JM, Dumont J, Montagnon B, Asselain B, Daniel MT, Flandrin G (1980) Leucémies aiguës myéloblastiques survenant au cours de l’évolution de lymphomes malins nonhodgkiniens. Nouv Presse Med 9: 3513–3516.

    PubMed  CAS  Google Scholar 

  • Hemminki K (1984) Reactions of ethyleneimine with guanosine and deoxyguanosine. Chem Biol Interact 48: 249–260.

    Article  PubMed  CAS  Google Scholar 

  • Henderson BE, Ross R, Bernstein L (1988) Estrogens as a cause of human cancer: the Richard and Hinda Rosenthal Foundation Award Lecture. Cancer Res 48: 246–253.

    PubMed  CAS  Google Scholar 

  • Herbst AL, Scully RE (1970) Adenocarcinoma of the vagina in adolescence. A report of 7 cases including 6 clear-cell carcinomas (so-called mesonephromas). Cancer 25: 745–757.

    Article  PubMed  CAS  Google Scholar 

  • Herbst AL, Kurman RJ, Scully RE, Poskanzer DC (1972) Clear-cell adenocarcinoma of the genital tract in young females. Registry report. N Engl J Med 287: 1259–1264.

    Google Scholar 

  • Heston WE (1949) Induction of pulmonary tumors in strain A mice with methylbis(β-chloroethyl)amine hydrochloride. JNCI 10: 125–140.

    Google Scholar 

  • Highman B, Norvell M J, Shellenberger TE (1977) Pathological changes in female C3H mice continuously fed diets containing diethylstilbestrol or 17β-estradiol. J Environ Pathol Toxicol 1: 1–30.

    CAS  Google Scholar 

  • Hinson J A, Mitchell JR (1976) N-Hydroxylation of phenacetin by hamster liver microsomes. Drug Metab Dispos 4: 430–435.

    PubMed  CAS  Google Scholar 

  • Hooker CW, Pfeiffer CA (1942) The morphology and development of testicular tumors in mice of the A strain receiving estrogens. Cancer Res 2: 759–769.

    Google Scholar 

  • International Agency for Research on Cancer (1974) Evaluation of the carcinogenic risk of chemicals to humans: some aromatic amines, hydrazine and related substances, N-nitroso compounds and miscellaneous alkylating agents. IARC Monographs 4: 247–252.

    Google Scholar 

  • International Agency for Research on Cancer (1976) Evaluation of the carcinogenic risk of chemicals to man: some miscellaneous pharmaceutical substances. IARC Monographs 13

    Google Scholar 

  • International Agency for Research on Cancer (1979) Evaluation of the carcinogenic risk of chemicals to man: sex hormones II. IARC Monographs 21: 173–231.

    Google Scholar 

  • International Agency for Research on Cancer (1980) Evaluation of the carcinogenic risk of chemicals to man: some pharmaceutical drugs. IARC Monographs 24: 297–314.

    Google Scholar 

  • International Agency for Research on Cancer (1981) Evaluation of the carcinogenic risk of chemicals to humans: some antineoplastic and immunosuppressive agents. IARC Monographs 26: 165–202.

    Google Scholar 

  • International Agency for Research on Cancer (1982) Evaluation of the carcinogenic risk of chemicals to humans: chemicals, industrial processes and industries associated with cancer in humans. IARC Monographs [Suppl] 4: 173–205.

    Google Scholar 

  • International Agency for Research on Cancer (1985) Evaluation of the carcinogenic risk of chemicals to humans: cross index of synonyms and trade names in volumes 1 to 36. IARC Monographs [Suppl] 5

    Google Scholar 

  • International Agency for Research on Cancer (1987a) Evaluation of the carcinogenic risk of chemicals to humans: silica and some silicates. IARC Monographs 42:13–32, 265–289

    Google Scholar 

  • International Agency for Research on Cancer (1987 b) Evaluation of the carcinogenic risk of chemicals to humans: overall evaluations of carcinogenicity: an updating of IARC Monographs vol 1–42. IARC Monographs [Suppl] 7:310–312,330–332.

    Google Scholar 

  • Isaka H, Yoshii H, Otsuji A, Koike M, Nagai Y, Koura M, Sugiyasu K, Kanabayashi T (1979) Tumors of Sprague-Dawley rats induced by long-term feeding of phenacetin. Gann 70: 29–36.

    PubMed  CAS  Google Scholar 

  • Isomäki HA, Hakulinen T, Joutsenlahti U (1978) Excess risk of lymphomas, leukemia and myeloma in patients with rheumatoid arthritis. J Chron Dis 31: 691–696.

    Article  PubMed  Google Scholar 

  • Jensen DE, Magee PN (1981) Methylation of DNA by nitrosocimetidine in vitro. Cancer Res 41: 230–236.

    PubMed  CAS  Google Scholar 

  • Jensen DE, Stelman GJ, Spiegel A (1987) Species differences in blood-mediated nitrosocimetidine denitrosation. Cancer Res 47: 353–359.

    PubMed  CAS  Google Scholar 

  • Kallama S, Hemminki K (1984) Alkylation of guanosine by phosphoramide mustard, chloromethine hydrochloride and chlorambucil. Acta Pharmacol Toxicol 54: 214–220.

    Article  CAS  Google Scholar 

  • Kinlen LJ (1985) Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. Am J Med 78 [Suppl 1 A]: 44–49.

    Article  PubMed  CAS  Google Scholar 

  • Kirkman H (1959) Estrogen-induced tumors of the kidney. IV. Incidence in female Syrian hamsters. Natl Cancer Inst Monogr 1: 59–75.

    PubMed  CAS  Google Scholar 

  • Kohn KW, Spears CL, Doty P (1966) Interstrand cross-linking of DNA by nitrogen mustard. J Mol Biol 19: 266–288.

    Article  PubMed  CAS  Google Scholar 

  • Kreis W (1970) Metabolism of an antineoplastic methylhydrazine derivative in a P815 mouse neoplasm. Cancer Res 30: 82–89.

    PubMed  CAS  Google Scholar 

  • Kyle RA (1984) Second malignancies associated with chemotherapy. In: Perry MC, Yarbro JW (eds) Toxicity of chemotherapy. Grune & Stratton, New York, pp 479–506.

    Google Scholar 

  • Lacassagne A (1938) Apparition d’adénocarcinomes mammaires chez des souris males traitées par une substance oestrogène synthétique. C R Soc Biol (Paris) 129: 641–643.

    CAS  Google Scholar 

  • LaRusso NF, Tomasz M, Müller M, Lipman R (1977) Interaction of metronidazole with nucleic acids in vitro. Mol Pharmacol 13: 872–882.

    PubMed  CAS  Google Scholar 

  • Law IP, Blom J (1977) Second malignancies in patients with multiple myeloma. Oncology 34: 20–24.

    Article  PubMed  CAS  Google Scholar 

  • Lawley PD (1984) Carcinogenesis by alkylating agents. In: Searle CE (ed) Chemical carcinogens, 2nd edn, vol I. ACS Monograph 182, Washington DC, pp 325–484.

    Google Scholar 

  • Lee PA, Kelly MR, Wallin JD (1976) Increased prolactin levels during reserpine treatment of hypertensive patients. J Am Med Assoc 235: 2316–2317.

    Article  CAS  Google Scholar 

  • Lijinsky W (1974) Reaction of drugs with nitrous acid as a source of carcinogenic nitrosamines. Cancer Res 34: 255–258.

    PubMed  CAS  Google Scholar 

  • Lijinsky W, Conrad E, Van de Bogart R (1972) Carcinogenic nitrosamines formed by drug/nitrite interactions. Nature 239: 165–167.

    Google Scholar 

  • Lindemann H, Harbers E (1980) In-vitro-Reaktion der drei alkylierenden Pharmaka Cyclophosphamid, Ifosfamid und Trofosfamid mit DNS und DNS-Bausteinen. Arzneimittelforsch 30: 2075–2080.

    Google Scholar 

  • Lipschütz A, Iglesias R, Panasevich VI, Salinas S (1967 a) Granulosa-cell tumours in mice by progesterone. Br J Cancer 21: 144–152.

    Google Scholar 

  • Lipschütz A, Iglesias R, Panasevich VI, Salinas S (1967 b) Pathological changes induced in the uterus of mice with the prolonged administration of progesterone and 19-nor-contraceptives. Br J Cancer 21: 160–165.

    Google Scholar 

  • Ludlum DB (1970) Properties of 7-methylguanine-containing templates for ribonucleic acid polymerase. J Biol Chem 245: 477–482.

    PubMed  CAS  Google Scholar 

  • Ludlum DB, Tong WP (1980) Crosslinking of DNA by busulfan. Formation of diguanyl derivatives. Biochim Biophys Acta 608: 174–181.

    Google Scholar 

  • Ludlum DB, Tong WP ( 1981 a) Modification of DNA and RNA bases. In: Prestayko AW, Crooke ST, Baker LH, Carter SK, Schein PS (eds) Nitrosoureas: current status and new developments. Academic, New York, pp 85–94.

    Google Scholar 

  • Ludlum DB, Tong WP (1981b) Modification of DNA and RNA bases by the nitrosoureas. In: Serrou B, Schein P, Imbach J-L (eds) Nitrosoureas in cancer treatment. Elsevier, Amsterdam, pp 21–31.

    Google Scholar 

  • Ludlum DB, Colinas RJ, Kirk MC, Mehta JR (1988) Reaction of reduced metronidazole with guanosine to form an unstable adduct. Carcinogenesis 9: 593–596.

    Article  PubMed  CAS  Google Scholar 

  • MacKenzie I (1955) The production of mammary cancer in rats using oestrogens. Br J Cancer 9: 284–299.

    Article  PubMed  CAS  Google Scholar 

  • Masiello P, Karunanayake EH, Bergamini E, Hearse DJ, Mellows G (1981) [14C] Strep-tozotocin: its distribution and interaction with nucleic acids and proteins. Biochem Pharmacol 30: 1907–1913.

    Google Scholar 

  • McClelland RA, Fuller JR, Seaman NE, Rauth AM, Battisteila R (1984) 2-Hydroxyl- aminoimidazoles: unstable intermediates in the reduction of 2-nitroimidazoles. Biochem Pharmacol 33: 303–309.

    Google Scholar 

  • Mehta JR, Przybylski M, Ludlum DB (1980) Alkylation of guanosine and deoxyguanosine by phosphoramide mustard. Cancer Res 40: 4183–4186.

    PubMed  CAS  Google Scholar 

  • Miller EC, Miller JA (1981) Searches for ultimate chemical carcinogens and reactions with cellular macromolecules. Cancer 47: 2327–2345.

    Article  PubMed  CAS  Google Scholar 

  • Mirkes PE, Fantel AG, Greenaway JC, Shepard TH (1981) Teratogenicity of cyclophosphamide metabolites: phosphoramide mustard, acrolein, and 4-ketocyclophosphamide in rat embryos cultured in vitro. Toxicol Appl Pharmacol 58: 322–330.

    Article  PubMed  CAS  Google Scholar 

  • Montgomery JA (1981) The development of the nitrosoureas: a study in congener synthesis. In: Prestayko AW, Crooke ST, Baker LH, Carter SK, Schein PS (eds) Nitrosoureas: current status and new developments. Academic, New York, pp 3–8.

    Google Scholar 

  • Mulder GJ, Kadlubar FF, Mays JB, Hinson JA (1984) Reaction of mutagenic phenacetin metabolites with glutathione and DNA: possible implications of toxicity. Molec Pharmacol 26: 342–347.

    CAS  Google Scholar 

  • Müller W, Brandis M (1981) Acute leukemia after cytotoxic treatment for nonmalignant disease in childhood: a case report and review of the literature. Eur J Pediatr 136: 105–108.

    Article  PubMed  Google Scholar 

  • Muradyan RY (1986 a) Experimental studies of phenacetin carcinogenicity. Vopr Onkol 32:63–70.

    Google Scholar 

  • Muradyan RY (1986 b) A study of possible carcinogenicity of reserpine. Vopr Onkol 32:76–81.

    Google Scholar 

  • Nakanishi K, Kurata Y, Oshima M, Fukushima S, Ito N (1982) Carcinogenicity of phenacetin: long-term feeding study in B6C3FJ mice. Int J Cancer 29: 439–444.

    Article  PubMed  CAS  Google Scholar 

  • National Cancer Institute (1978) Bioassay of phenoxybenzamine hydrochloride for possible carcinogenicity. NCI Carcinog Tech Rep Ser 72.

    Google Scholar 

  • National Cancer Institute (1979) Bioassay of procarbazine for possible carcinogenicity. NCI Carcinog Tech Rep Ser no 19.

    Google Scholar 

  • National Cancer Institute (1980) Bioassay of reserpine for possible carcinogenicity. Dept of Health, Education, and Welfare pub no (NIH) 80–1749.

    Google Scholar 

  • Nesnow S, Argus M, Bergman H, Chu K, Frith C, Helmes T, MeGaughty R, Ray V, Slaga TJ, Tennant R, Weisburger E (1986) Chemical carcinogens. A review and analysis of the literature of selected chemicals and the establishment of the gene-tox carcinogen data base. Mutat Res 185: 1–195.

    Google Scholar 

  • Noller KL, Decker DG, Lanier AP, Kurland LT (1972) Clear-cell adenocarcinoma of the cervix after maternal treatment with synthetic estrogens. Mayo Clin Proc 47: 629–630.

    PubMed  CAS  Google Scholar 

  • Ozawa N, Guengerich FP (1983) Evidence for formation of an S-[2-(N7-guanyl)ethyl]glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA. Proc Natl Acad Sei USA 80: 5266–5270.

    Article  CAS  Google Scholar 

  • Pan SC, Gardner WU (1948) Carcinomas of the uterine cervix and vagina in estrogen- and androgen-treated hybrid mice. Cancer Res 8: 337–341.

    PubMed  CAS  Google Scholar 

  • Penn I (1979) Tumor incidence in human allograft recipients. Transplant Proc 11: 1047–1051.

    PubMed  CAS  Google Scholar 

  • Poel WE (1969) Bioassays with inbred mice: their relevance for the random-bred animal. Prog Exp Tumor Res 11: 440–460.

    Google Scholar 

  • Prejean JD, Montgomery JA (1984) Structure-activity relationships in the carcinogenicity of anticancer agents. Drug Metab Rev 15: 619–646.

    Article  PubMed  CAS  Google Scholar 

  • Rao GS (1980) JV-Nitrosamines from drugs and nitrite: potential source of chemical carcinogens in humans? Pharm Int 1: 187–190.

    CAS  Google Scholar 

  • Reimer RR, Hoover R, Fraumeni JF Jr, Young RC (1977) Acute leukemia after alkylating-agent therapy of ovarian cancer. N Engl J Med 297: 177–181.

    Article  PubMed  CAS  Google Scholar 

  • Rustia M, Shubik P (1972) Induction of lung tumors and malignant lymphomas in mice by metronidazole. JNCI 48: 721–726.

    Google Scholar 

  • Rustia M, Shubik P (1979) Experimental induction of hepatomas, mammary tumors, and other tumors with metronidazole in noninbred Sas:MRC(Wl)BR rats. JNCI 63: 863–868.

    Google Scholar 

  • Rydberg B, Lindahl T (1982) Nonenzymatic methylation of DNA by the intracellular methyl group donor S-adenosyl-L-methionine is a potentially mutagenic reaction. Eur Molec Biol Organization 1: 211–216.

    CAS  Google Scholar 

  • Samson L (1986) The adaptive response of mammalian cells to alkylating damage and repair: see my implications for carcinogenesis and risk assessment. Plenum, New York, p 327

    Google Scholar 

  • Sander J, Bürkle G (1969) Induktion maligner Tumoren bei Ratten durch gleichzeitige Verfütterung von Nitrit und sekundären Aminen. Z Krebsforsch 73: 54–66.

    Article  PubMed  CAS  Google Scholar 

  • Schmähl D (1974) Investigation on the influence of immunodepressive means on the chemical carcinogenesis in rats. Z Krebsforsch 81: 211–215.

    Article  Google Scholar 

  • Schmähl D, Habs M (1979) Carcinogenic action of low-dose cyclophosphamide given orally to Sprague-Dawley rats in a lifetime experiment. Int J Cancer 23: 706–712.

    Article  PubMed  Google Scholar 

  • Schmähl D, Kaldor JM (1986) Carcinogenicity of alkylating cytostatic drugs. IARC publications no 78, Lyon.

    Google Scholar 

  • Schmähl D, Osswald H (1970) Experimentelle Untersuchungen über carcinogene Wirkungen von Krebs-Chemotherapeutica and Immunosuppressiva. Arzneimittelforsch 20: 1461–1467.

    PubMed  Google Scholar 

  • Schmähl D, Thomas C, Auer R (1977) Iatrogenic carcinogenesis. Springer-Verlag, Berlin Heidelberg New York

    Book  Google Scholar 

  • Shimkin MB, Weisburger JH, Weisburger EK, Gubareff N, Suntzeff V (1966) Bioassay of 29 alkylating chemicals by the pulmonary-tumor response in strain A mice. JNCI 36: 915–935.

    Google Scholar 

  • Singer B, Spengler SJ, Bodell WJ (1981) Tissue-dependent enzyme-mediated repair or removal of 0-ethyl pyrimidines and ethyl purines in carcinogen-treated rats. Carcinogenesis 2: 1069–1073.

    Article  PubMed  CAS  Google Scholar 

  • Skibba JL, Bryan GT (1971) Methylation of nucleic acids and urinary excretion of Relabeled 7-methylguanine by rats and man after administration of 4(5)-(3,3-dimethyl-l- triazeno)imidazole 5(4)-carboxamide. Toxicol Appl Pharmacol 18: 707–719.

    Article  PubMed  CAS  Google Scholar 

  • Smithline F, Sherman L, Kolodny HD (1975) Prolactin and breast carcinoma. N Engl J Med 292: 784–792.

    Article  PubMed  CAS  Google Scholar 

  • Stoner GD, Shimkin MB, Kniazeff AJ, Weisburger JH, Weisburger EK, Gori GB (1973) Test for carcinogenicity of food additives and chemotherapeutic agents by the pulmonary tumor response in strain A mice. Cancer Res 13: 3069–3085.

    Google Scholar 

  • Stott H, Fox W, Girling DJ, Stephens RJ, Galton DAG (1977) Acute leukaemia after busulfan. Br Med 12: 1513–1517.

    Article  Google Scholar 

  • Struck RF, Kirk MC, Witt MH, Laster WR Jr (1975) Isolation and mass spectral identification of blood metabolites of cyclophosphamide: evidence for phosphoramide mustard as the biologically active metabolite. Biomed Mass Spectrom 2: 46–52.

    Article  PubMed  CAS  Google Scholar 

  • Thiede T, Christiensen BC (1969) Bladder tumors induced by chlornaphazine. Acta med Scand 185: 133–137.

    Article  PubMed  CAS  Google Scholar 

  • Tomasz M (1970) Novel assay of 7-alkylation of guanine residues in DNA. Application to nitrogen mustard, triethylenemelamine and mitomycin C. Biochem Biophys Acta 213: 288–295.

    PubMed  CAS  Google Scholar 

  • Tong WP, Ludlum DB (1980) Crosslinking of DNA by busulfan: formation of diguanyl derivatives. Biochim Biophys Acta 608: 174–181.

    PubMed  CAS  Google Scholar 

  • Tong WP, Ludlum DB (1981) Formation of the cross-linked base, diguanylethane, in DNA treated with N,N’-bis(2-chloroethyl)-N-nitrosourea. Cancer Res 41: 380–382.

    Google Scholar 

  • Tong WP, Kirk MC, Ludlum DB ( 1982 a) Formation of the crosslink, l-[N3-deoxycytidyl]2-[N1-deoxyguanosinyllethane, in DNA treated with N,N’-bis(2-chloroethyl)-N- nitrosourea ( BCNU ). Cancer Res 42: 3102–3105.

    Google Scholar 

  • Tong WP, Kohn KW, Ludlum DB (1982 b) Modifications of DNA by different haloethyl-nitrosoureas. Cancer Res 42: 4460–4464.

    Google Scholar 

  • Trentin J.J. (1954) Effect of long-term treatment with high levels of progesterone on the incidence of mammary tumors in mice. Proc Am Assoc Cancer Res 1: 50.

    Google Scholar 

  • United States Government Department of Health and Human Services (1985) Fourth annual report in carcinogens. National Toxicology Program, Bethesda, MD, 78–1317.

    Google Scholar 

  • Varghese AJ, Whitmore GF (1981) Cellular and chemical reduction products of misonidazole. Chem Biol Interactions 36: 141–151.

    Article  CAS  Google Scholar 

  • Varghese AJ, Whitmore GF (1983) Modification of guanine derivatives by reduced 2-nitroimidazoles. Cancer Res 43: 78–82.

    PubMed  CAS  Google Scholar 

  • Vaught JB, McGarvey PB, Lee MS, Garner CD, Wang CY, Linsmaier-Bednar EM, King CM (1981) Activation of TV-hydroxyphenactin to mutagenic and nucleic acid-binding metabolites by acyl transfer, deacylation, and sulfate conjugation. Cancer Res 41: 3424–3429.

    PubMed  CAS  Google Scholar 

  • Verdeal K, Ertiirk E, Rose DP (1983) Effects of reserpine administration on rat mammary tumors and uterine disease induced by N-nitrosomethylurea. Eur J Can Clin Oncol 19: 825–834.

    Article  CAS  Google Scholar 

  • Vu VT, Fenselau CC, Colvin OM (1981) Identification of three alkylated nucleotide adducts from the reaction of guanosine 5’-monophosphate with phosphoramide mustard. J Am Chem Soc 103: 7362–7364.

    Article  CAS  Google Scholar 

  • Weisburger EK (1977) Bioassay program for carcinogenic hazards of cancer chemothera¬peutic agents. Cancer 40: 1935 - 1951.

    Article  PubMed  CAS  Google Scholar 

  • Weisburger JH, Griswold DP, Prejean JD, Casey AE, Wood HB, Weisburger EK (1975) The carcinogenic properties of some of the principal drugs used in clinical cancer chemotherapy. Recent Results Cancer Res 52: 1–17.

    PubMed  CAS  Google Scholar 

  • Welsch CW, Adams C, Lambrecht LK, Hassett CC, Brooks CL (1977) 17£-Oestradiol and enovid mammary tumorigenesis in C3H/HeJ female mice: counteraction by concurrent 2-bromo-α-ergocryptine. Br J Cancer 35: 322–328.

    Google Scholar 

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Authors
  1. D. B. Ludlum
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Editors and Affiliations

  1. Chester Beatty Laboratories, The Institute of Cancer Research: Royal Cancer Hospital, Fulham Road, SW3 6JB, London, Great Britain

    Colin S. Cooper Ph.D.  & Philip L. Grover D.Sc.  & 

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© 1990 Springer-Verlag Berlin Heidelberg

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Ludlum, D.B. (1990). Therapeutic Agents as Potential Carcinogens. In: Cooper, C.S., Grover, P.L. (eds) Chemical Carcinogenesis and Mutagenesis I. Handbook of Experimental Pharmacology, vol 94 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74775-5_5

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  • DOI: https://doi.org/10.1007/978-3-642-74775-5_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74777-9

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