Skip to main content
SpringerLink
Log in

Anthracycline Antitumor Antibiotics: Their Carcinogenicity and their Mutagenicity

  • Chapter
Anthracycline Antibiotics in Cancer Therapy

Part of the book series: Developments in Oncology ((DION,volume 10))

Abstract

The long-term toxicity of antitumor agents, i.e., their oncogenicity and their mutagenicity, is a subject of growing concern because of the increased survival of cancer patients which modern chemotherapy has made possible. It has been one of the intriguing results of cancer research that many active antineoplastic agents have been found to be carcinogenic. It is now well established that many antitumor substances are oncogenic in cells in culture (1) and in laboratory animals (2, 3); and, from observations in patients being given such compounds for nonmalignant diseases and after transplantation surgery as well as from the occurrence of second neoplasms after chemotherapy of a primary neoplasm, it can be suspected that many are also carcinogenic in man (4). This report attempts to consolidate the available data on the genotoxic effects of one important class of antitumor agents, i.e., the anthracycline antibiotics.

Direct correspondence to this author.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Marquardt H and Marquardt H. 1977. Induction of malignant transformation and mutagenesis in cell cultures by Cancer chemotherapeutic agents. Cancer, 40: 1930–1934.

    Article  PubMed  CAS  Google Scholar 

  2. Sieber SM and Adamson RH. 1975. The clastogenic, mutagenic, teratogenic and carcinogenic effects of various antineoplastic agents. In “Pharmacological Basis of Cancer Chemotherapy”, Williams and Wilkins Publ., Baltimore, pp. 401–468.

    Google Scholar 

  3. Sieber SM and Adamson RH. 1975. Toxicity of antineoplastic agents in man: Chromosomal aberrations, antifertility effects, congenital malformations and carcinogenic potential. Adv. Cancer Res., 22: 57–155.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  5. Bertazzoli C, Chieli T,and Solcia E. 1971. Different incidence of breast carcinomas or fibroadenomas in daunomycin or adriamycin treated rats. Experienta, 27: 1209–121.

    Article  CAS  Google Scholar 

  6. Sternberg SS, Philips FS, and Cronin AP. 1972. Renal tumors and other lesions following a single intravenous injection of daunomycin. Cancer Res., 32: 1029–1036.

    PubMed  CAS  Google Scholar 

  7. Philips FS, Gilladoga A, Marquardt H, Sternberg SS, and Vidal PM. 1975. Some observations on the toxicity of adriamycin. Cancer Chemotherap. Rep. Part 3, 6: 177–181.

    CAS  Google Scholar 

  8. Marquardt H, Philips FS, and Sternberg SS. 1976. Tumorigenicity in vivo and induction of malignant transformation and mutagenesis in cell cultures by adriamycin and daunomycin. Cancer Res., 36: 2065–2069.

    PubMed  CAS  Google Scholar 

  9. Bucciarelli E. 1981. Mammary tumor induction in male and female Sprague-Dawley rats by adriamycin and daunomycin. J. Natl. Cancer Inst., 66: 81–84.

    CAS  Google Scholar 

  10. Shellabarger CJ, Bond VP, and Cronkite EP. 1960. Studies on radiation-induced mammary gland neoplasia in the rat. Rad. Res.,. 13: 242–249.

    Article  CAS  Google Scholar 

  11. Philips FS and Sternberg SS. 1975. Tests for tumor induction by antitumor agents. Recent Results Cancer Res., 52: 29–35.

    Article  PubMed  CAS  Google Scholar 

  12. Price PJ, Su WA, Skeen PC, Chirigos MA, and Huebner RJ. 1975. Transforming potential of the antiCancer drug adriamycin. Science, 187: 1200–1201.

    Article  PubMed  CAS  Google Scholar 

  13. Bertazzoli C, Sala L, Solicia E, and Ghione M. 1975. Experimental adriamycin cardiotoxicity prevented by ubiquinone in vivo in rabbits. IRCS Med. Science, 3: 468.

    CAS  Google Scholar 

  14. Notman J, Marquardt H, and Zedeck MS. 1980. Cardiac effects and tumor induction in rats receiving a single injection of adriamycin with and without treatment with cysteamine. Proc. Amer. Assoc. Cancer Res., 21: 309.

    Google Scholar 

  15. Marquardt H, Sapozink MD, and Zedeck MS. 1974. Inhibition by cysteamine-HCl of oncogenesis induced by 7,12-dimethylbenz (a) anthracene without affecting toxicity. Cancer Res., 34: 3387–3390.

    PubMed  CAS  Google Scholar 

  16. Miller EC. 1978. Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential address. Cancer Res., 38: 1479–1496.

    PubMed  CAS  Google Scholar 

  17. Marquardt H, Baker S, Grab D, and Marquardt H. 1977. Oncogenic and mutagenic activity of adriamycin decreased by microsomal metabolism. Proc. Amer. Assoc. Cancer Res., 18: 13.

    Google Scholar 

  18. Di Marco A and Arcamone F. 1975. DNA-complexing antibiotics: Daunomycin, adriamycin and their derivatives. Arzneimittelforsch., 25: 368–375.

    PubMed  CAS  Google Scholar 

  19. Di Marco A, Zunino F, Orezzi P,and Gambetta R. 1972. Interaction of daunomycin with nucleic acids: Effect of photoirradiation of the complex. Experientia, 28: 327–328.

    Article  Google Scholar 

  20. Ames BN, McCann J, and Yamasaki E. 1975. Methods for detecting carcinogens and mutagens with the Salmonella/ mammalian microsome mutagenicity test. Mutat. Res., 31 347–364.

    PubMed  CAS  Google Scholar 

  21. Scornik OA, Hoagland MB, Pfefferkorn LC, and Bishop EA. 1967. Inhibition of protein synthesis in rat liver microsome fractions. J. Biol. Chem., 242: 131–139.

    PubMed  CAS  Google Scholar 

  22. Ghezzi P, Donelli MG, Pantarotto C, Facchinetti T, and Garattini S. 1981. Evidence for covalent binding of adriamycin to rat liver microsomal proteins. Biochem. Pharmacol., 30: 175–177.

    Article  PubMed  CAS  Google Scholar 

  23. Vig BK. 1977. Genetic toxicology of mitomycin C, actinomycins, daunomycin and adriamycin. Mutat.Res., 49: 189–238.

    Google Scholar 

  24. Schwartz HS. 1975. DNA breaks in P-288 tumor cells in mice after treatment with daunorubicin and adriamycin. Res. Commun. Chem. Pathol. Pharmacol., 10: 51–64.

    PubMed  CAS  Google Scholar 

  25. Lee YC and Byfield JE. 1976. Induction of DNA degradation in vivo by adriamycin. J. Natl. Cancer Inst., 57: 221–224.

    PubMed  CAS  Google Scholar 

  26. Kusyk CJ and Hsu TC. 1976. Adriamycin-induced chromosome damage: Elevated frequencies of isochromatid aberrations in G2 and S phases. Experientia, 32: 1513–1514.

    Article  PubMed  CAS  Google Scholar 

  27. Fialkoff H, Goodman MF, and Seraydarian MW. 1979. Differential effect of adriamycin on DNA replicative and repair synthesis in cultured neonatal rat cardiac cells. Cancer Res., 39: 1321–1327.

    PubMed  CAS  Google Scholar 

  28. Anderson WA, Moreau PL, and Devoret R. 1980. Induction of prophage A by daunorubicin and derivatives. Correlation with antineoplastic activity. Mutat. Res., 77: 197–208.

    Article  PubMed  CAS  Google Scholar 

  29. Montesano R, Bartsch H, and Tomatis L (eds.). 1980. Longterm and short-term screening assays for carcinogens: A critical appraisal. IARC Monographs, Supplement 2, IARC, Lyon; pp. 210–211.

    Google Scholar 

  30. Pani B, Monti-Bragadin C, and Samer L. 1975. Effect of excision repair system on antibacterial and mutagenic activity of daunomycin and other intercalating agents in Salmonella typhimurium. Experientia, 31: 787–788.

    Article  PubMed  CAS  Google Scholar 

  31. Marquardt H. 1978. Chemical oncogenesis: Mammalian cell culture studies. Staub-Reinhaltung der Luft, 38: 258–265.

    CAS  Google Scholar 

  32. Seino Y, Nagao M, Yahagi T, Hoshi A, Kawachi T, and Sugimura T. 1978. Mutagenicity of several classes of antitumor agents to Salmonella typhimurium TA98, TA100, and TA92. Cancer Res., 38: 2148–2156.

    PubMed  CAS  Google Scholar 

  33. Hannan MA and Nasim A. 1978. Mutagenicity and recombinogenicity of daunomycin in Saccharomyces cerevisiae. Cancer Letters, 5: 319–324.

    Article  PubMed  CAS  Google Scholar 

  34. Di Marco A, Casazza AM, and Pratesi G. 1977. Antitumor activity of 4-demethoxydaunorubicin administered orally. Cancer Treatment Reports, 61: 893–894.

    PubMed  Google Scholar 

  35. Marquardt H, Philips FS, Marquardt H, and Sternberg SS. 1979. Oncogenicity of 4-demethoxydaunomycin: Lack of correlation among in vitro short-term tests and between in vitro and in vivo findings. Proc. Amer. Assoc. Cancer Res., 20: 45.

    Google Scholar 

  36. Plumbridge TW and Brown JR. 1978. Studies on the mode of interaction of 4-epi-adriamycin and 4-demethoxydaunomycin with DNA. Biochem.Pharmacol., 27: 1881–1882.

    Article  PubMed  CAS  Google Scholar 

  37. Tong GL, Henry OW, and Acton EM. 1979. 5-Iminodaunorubicin. Reduced cardiotoxic properties in an antitumor anthracycline. J. med. Chem., 22: 34–40.

    Google Scholar 

  38. Li LH, Kuentzel SL, Murch LL, Pschigoda LM, and Krueger WC. 1979. Comparative biological and biochemical effects of nogalamycin and its analogs on L1210 leukemia. Cancer Res., 39: 4816–4822.

    PubMed  CAS  Google Scholar 

  39. Gause GF, Brazhnikova MG, and Shorin VA. 1974. A new antitumor antibiotic, carminomycin. Cancer Chemotherapy Reports (Part 1), 58: 255–256.

    CAS  Google Scholar 

  40. Hori S, Shirai M, Hirano S, Oki T, Inui T, Tsukagoshi S, Ishizuka M, Takeuchi T, and Umezawa H. 1977. Antitumor activity of new anthracycline antibiotics, aclacinomycinA and its analogs, and their toxicity. Gann, 68: 685–690.

    PubMed  CAS  Google Scholar 

  41. Oki T, Takeuchi T, Oka S, and Umezawa H. 1980. Current status of Japanese studies with the new anthracycline antibiotic aclacinomycinA. Recent Res. Cancer Res., 74 207–216.

    Article  CAS  Google Scholar 

  42. Oki T, Takeuchi T, Oka S, and Umezawa H. 1981. New anthracycline antibiotic aclacinomycinA: Experimental studies and correlations with clinical trials. Recent Res. Cancer Res., 76: 21–40.

    CAS  Google Scholar 

  43. Umezawa K, Sawamura M, Matsushima T, and Sugimura T. 1978. Mutagenicity of aclacinomycinA and daunomycin derivatives. Cancer Res., 38: 1782–1784.

    PubMed  CAS  Google Scholar 

  44. Marquardt H. 1979. DNA #x2014; The critical target in chemical carcinogenesis? In:“Chemical Carcinogens and DNA#x201D;, Grover PL (ed.), CRC Press, Inc., Boca Raton, Florida; pp 159–179.

    Google Scholar 

  45. Tong GL, Wu HY, Smith TH, and Henry OW. 1979. Adriamycin analogs. 3. Synthesis of N-alkylated anthracyclines with enhanced efficacy and reduced cardiotoxicity. J. med. Chem., 22: 912–918.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. J. Westendorf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hildegard Marquardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hans Marquardt
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. New York University Medical Center, New York, New York, 10016, USA

    Franco M. Muggia

  2. Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA

    Charles W. Young

  3. Northern California Oncology Group, Palo Alto, California, 94304, USA

    Stephen K. Carter

Rights and permissions

Reprints and permissions

Copyright information

© 1982 Martinus Nijhoff Publishers, The Hague

About this chapter

Cite this chapter

Westendorf, J., Marquardt, H., Marquardt, H. (1982). Anthracycline Antitumor Antibiotics: Their Carcinogenicity and their Mutagenicity. In: Muggia, F.M., Young, C.W., Carter, S.K. (eds) Anthracycline Antibiotics in Cancer Therapy. Developments in Oncology, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-7630-6_3

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-7630-6_3

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-009-7632-0

  • Online ISBN: 978-94-009-7630-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation