Targets of Chemotherapeutic Drug Action in Testis and Epididymis

  • Bernard Robaire
  • Barbara F. Hales
Part of the Serono Symposia USA Norwell, Massachusetts book series (SERONOSYMP)

Abstract

Paternal occupational exposures to mercury, anaesthetic gases, lead, some solvents, and pesticides are associated with an increase in spontaneous abortions (1). Paternal occupations that include painters, auto mechanics, and firemen and involve exposure to metals, solvents, and pesticides are associated with birth defects (2). Adverse effects may not be apparent at birth; increased incidences of childhood cancer are found after a number of the same exposures as for birth defects (3).

Keywords

Morphine Androgen Cyclophosphamide Thymidine Infertility 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Savitz DA, Sonnenfeld NL, Olshan AF. Review of epidemiologic studies of paternal occupational exposure and spontaneous abortion. Am J Ind Med 1994;25:361–83.PubMedCrossRefGoogle Scholar
  2. 2.
    Olshan AF, Teschke K, Baird PA. Paternal occupation and congenital anomalies in offspring. Am J Ind Med 1991;20:447–75.PubMedCrossRefGoogle Scholar
  3. 3.
    Kuijten RR, Bunin GR, Nass CC, Meadows AT. Parental occupation and childhood astrocytoma: results of a case-control study. Cancer Res 1992;52:782–6.PubMedGoogle Scholar
  4. 4.
    Soyka LF, Peterson JM, Joffe JM. Lethal and sublethal effects on the progeny of male rats treated with methadone. Toxicol Appl Pharmacol 1978;45:797–807.PubMedCrossRefGoogle Scholar
  5. 5.
    Lutwak-Mann C. Observations on the progeny of thalidomide-treated male rabbits. Br Med J 1964;1:1090–1.PubMedCrossRefGoogle Scholar
  6. 6.
    Hales BF, Smith S, Robaire B. Cyclophosphamide in the seminal fluid of treated males: transmission to females by mating and effects on progeny outcome. Toxicol Appl Pharmacol 1986;84:423–30.PubMedCrossRefGoogle Scholar
  7. 7.
    Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, Wilson EM. Persistent DDT metabolite p, p’-DDE is a potent androgen receptor antagonist. Nature (Lond) 1995;375:581–5.CrossRefGoogle Scholar
  8. 8.
    Klinefelter GR, Laskey JW, Roberts NL. In vitro/in vivo effects of ethane di-methanesulfonate on Leydig cells of adult rats. Toxicol Appl Pharmacol 1991; 107: 460–71.PubMedCrossRefGoogle Scholar
  9. 9.
    Kleeman JM, Moore RW, Peterson RE. Inhibition of testicular steroidogenesis in 2,3,7,8-tetrachloro-p-dioxin treated rats: evidence that the key lesion occurs prior to or during pregnenolone formation. Toxicol Appl Pharmacol 1990; 106:112–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Hall ES, Hall SJ, Boekelheide K. 2,5-Hexanedione exposure alters microtubule motor distribution in adult rat testis. Fundam Appl Toxicol 1995;24:173–82.PubMedCrossRefGoogle Scholar
  11. 11.
    Chellman GJ, Bus JS, Working PK. Role of epididymal inflammation in the induction of dominant lethal mutations in Fischer 344 rat sperm by methyl chloride. Proc Natl Acad Sci USA 1986;83:8087–91.PubMedCrossRefGoogle Scholar
  12. 12.
    Chellman GJ, Morgan KT, Bus JS, Working PG. Inhibition of methyl chloride toxicity in male F-344 rats by the anti-inflammatory agent BW755C. Toxicol Appl Pharmacol 1986;85:367–79.PubMedCrossRefGoogle Scholar
  13. 13.
    Qiu J, Hales BF, Robaire B. Adverse effects of cyclophosphamide on progeny outcome can be mediated through post-testicular mechanisms in the rat. Biol Reprod 1992; 46:926–31.PubMedCrossRefGoogle Scholar
  14. 14.
    Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogenic renewal. Physiol Rev 1972;52:198–236.PubMedGoogle Scholar
  15. 15.
    Russell LB. Effects of spermatogenic cell type on quantity and quality of mutations. In: Mattison DR, Olshan AF, eds. Male-mediated developmental toxicity New York: Plenum Press, 1994:37–48.CrossRefGoogle Scholar
  16. 16.
    Trasler JM, Hales BF, Robaire B. Paternal cyclophosphamide treatment of rats causes fetal loss and malformations without affecting male fertility Nature (Lond) 1985; 316:144–6.CrossRefGoogle Scholar
  17. 17.
    Trasler JM, Hales BF, Robaire B. Chronic low dose cyclophosphamide treatment of adult male rats: effect on fertility, pregnancy outcome and progeny. Biol Reprod 1986:34:275–83.PubMedCrossRefGoogle Scholar
  18. 18.
    Kangasniemi M, Wilson G, Parchuri N, Huhtaniemi I, Meistrich ML. Rapid protection of rat spermatogenic stem cells against procarbazine by treatment with gonadotropin-releasing hormone antagonist (Nal-Glu) and an antiandrogen (flutamide). Endocrinology 1995;136:2881–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Trasler JM, Hales BF, Robaire B. A time course study of chronic paternal cyclophosphamide treatment in rats: effects on pregnancy outcome and the male reproductive and hematologic systems. Biol Reprod 1987;37:317–326.PubMedCrossRefGoogle Scholar
  20. 20.
    Anderson D, Bishop JB, Garner RC, Ostrosky-Wegman P, Selby PB. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat Res 1995;330:115–81.PubMedCrossRefGoogle Scholar
  21. 21.
    Fabricant JD, Legator MS, Adams PM. Post-meiotic cell mediation of behavior in progeny of male rats treated with cyclophosphamide. Mutat Res 1983;119:185–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Generoso WM, Cattanach B, Malashenko AM. Mutagenicity of selected chemicals in mammals; the heritable translocation test. In: de Serres FJ, Shelby MD, eds. Comparative chemical mutagenesis. New York: Plenum Press, 1981:681–707.Google Scholar
  23. 23.
    Backer LC, Gibson MJ, Moses MJ, Allen JW. Synaptonemal complex damage in relation to meiotic chromosome aberration after exposure of male mice to cyclophosphamide. Mutat Res 1988;203:317–30.PubMedGoogle Scholar
  24. 24.
    Sotomayor RE, Cumming RB. Induction of translocations by cyclophosphamide in different germ cell stages of male mice: cytological characterization and transmission. Mutat Res 1975;27:375–88.PubMedCrossRefGoogle Scholar
  25. 25.
    Hales BF, Robaire B. Reversibility of the effects of chronic paternal exposure to cyclophosphamide on pregnancy outcome in rats. Mutat Res 1990;229:129–34.PubMedCrossRefGoogle Scholar
  26. 26.
    Hales BF, Crosman K, Robaire B. Increased postimplantation loss and malformations among the F2 progeny of male rats chronically treated with cyclophosphamide. Teratology 1992;45:671–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Auroux M, Dulioust EJB, Nawar NNY, Yacoub SG, Mayaux MJ, Schwartz D, et al. Antimitotic drugs in male rat. Behavioral abnormalities in the second generation. J Androl 1988;9:153–9.PubMedGoogle Scholar
  28. 28.
    Auroux M, Dulioust E, Selva J, Rince R Cyclophosphamide in the F0 male rat: physical and behavioral changes in three successive adult generations. Mutat Res 1990;229:189–200.PubMedCrossRefGoogle Scholar
  29. 29.
    Cai L, Hales BF, Robaire B. Induction of apoptosis in the germ cells of adult male rats after exposure to cyclophosphamide. Biol Reprod 1997;56:1490–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Naish SJ, Perreault SD, Zirkin BR. DNA synthesis in the fertilizing hamster sperm nucleus: sperm template availability and egg cytoplasmic control. Biol Reprod 1987;36:245–53.PubMedCrossRefGoogle Scholar
  31. 31.
    Perreault SD, Naish SJ, Zirkin BR. The timing of hamster sperm nuclear decondensation and male pronucleus formation is related to sperm nuclear disulfide bond content. Biol Reprod 1987;36:239–44.PubMedCrossRefGoogle Scholar
  32. 32.
    Perreault SD, Zirkin BR. Sperm nuclear decondensation in mammals: role of sperm-associated proteinase in vivo. J Exp Zool 1982;224:253–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Perreault SD, Barbee RR, Elstein KH, Zucker RM, Keefer CL. Interspecies differences in the stability of mammalian sperm nuclei assessed in vivo by sperm microinjection and in vitro by flow cytometry. Biol Reprod 1988;39:157–67.PubMedCrossRefGoogle Scholar
  34. 34.
    Qiu JP, Hales BF, Robaire B. Effects of chronic low dose cyclophosphamide exposure on the nuclei of rat spermatozoa. Biol Reprod 1995;52:33–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Sega GA, Owens JG. Methylation of DNA and protamine by methyl methanesulfonate in the germ cells of male mice. Mutat Res 1983; 111:227–44.PubMedCrossRefGoogle Scholar
  36. 36.
    Sega GA, Valdivia Alcota RP, Tancongco CP, Brimer PA. Acrylamide binding to DNA and protamine of spermiogenic stages in the mouse and its relationship to genetic damage. Mutat Res 1989;216:221–30.PubMedGoogle Scholar
  37. 37.
    Allen JW, Collins BW, Cannon RE, McGregor PW, Afshari A, Fuscoe JC. Aneuploidy tests: cytogenetic analysis of mammalian male germ cells. In: Mattison DR, Olshan AF, eds. Male-mediated developmental toxicity. New York: Plenum Press, 1994:59–69.CrossRefGoogle Scholar
  38. 38.
    Martin RH, Rademaker A. The effect of age on the frequency of sperm chromosomal abnormalities in normal men. Am J Hum Genet 1987;41:484–92.PubMedGoogle Scholar
  39. 39.
    Wyrobeck AJ, Robbins AW, Mehraein Y, Pinkel D, Weier H-U. Detection of sex chromosomal aneuploidies X-X, Y-Y, and X-Y in human sperm using two-chromosome fluorescence in situ hybridization. Am J Med Genet 1994;53:1–7.CrossRefGoogle Scholar
  40. 40.
    Martin RH, Rademaker AW, Leonard NJ. Analysis of chromosomal abnormalities in human sperm after chemotherapy by karyotyping and fluorescence in situ hybridization (FISH). Cancer Genet Cytogenet 1995;80:29–32.PubMedCrossRefGoogle Scholar
  41. 41.
    Qiu J, Hales BF, Robaire B. Damage to rat spermatozoal DNA after chronic cyclophosphamide exposure. Biol Reprod 1995;53:1465–73.PubMedCrossRefGoogle Scholar
  42. 42.
    Kohn KW, Erickson LC, Ewig RAG, Friedman CA. Fractionation of DNA from mammalian cells by alkaline elution. Biochemistry 1976;15:4629–37.PubMedCrossRefGoogle Scholar
  43. 43.
    Ram PT, Schultz RM. Reporter gene expression in G2 of the 1 -cell embryo. Dev Biol 1993;156:552–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Worrad DM, Ram PT, Schultz RM. Regulation of gene expression in the mouse oocyte and early preimplantation embryo: developmental changes in Spl and TATA box-binding protein, TBP Development (Camb) 1994;120:2347–57.Google Scholar
  45. 45.
    Favor J. Specific-locus mutation tests in germ cells of the mouse: an assessment of the screening procedures and the mutational events detected. In: Mattison DR, Olshan AF, eds. Male-mediated developmental toxicity. New York, Plenum Press: 1994:23–36.CrossRefGoogle Scholar
  46. 46.
    Austin (Kelly) SM, Robaire B, Hales BF. Paternal cyclophosphamide exposure causes decreased cell proliferation in cleavage-stage embryos. Biol Reprod 1994;50:55–64.PubMedCrossRefGoogle Scholar
  47. 47.
    Ward WS, Coffey DS. Specific organization of genes in relation to the sperm nuclear matrix. Biochem Biophys Res Commun 1990;173:20–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Bentley KS, Sarrif AM, Cimino MC, Auletta AE. Assessing the risk of heritable gene mutation in mammals: Drosophila sex-linked recessive lethal test and tests measuring DNA damage and repair in mammalian germ cells. Environ Mol Mutagen 1994;23:3–11.PubMedCrossRefGoogle Scholar
  49. 49.
    Sotomayor RE, Sega GA, Cumming RB. Unscheduled DNA synthesis in spermatogenic cells of mice treated in vivo with the indirect alkylating agents cyclophosphamide and mitomen. Mutat Res 1978;50:229–40.PubMedCrossRefGoogle Scholar
  50. 50.
    Walter CA, Trolian DA, McFarland MB, Street KA, Gurram GR, McCarrey JR. Xrcc-1 expression during male meiosis in the mouse. Biol Reprod 1996;55:630–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Xanthoudakis S, Smeyne RJ, Wallace FD, Curran T. The REDOX/DNA repair protein, ref-1, is essential for early embryonic development in mice. Proc Natl Acad Sci USA 1996;93:8919–23.PubMedCrossRefGoogle Scholar
  52. 52.
    Edelmann W, Cohen PE, Kane M, Lau K, et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell 1996;85:1 125–34.CrossRefGoogle Scholar
  53. 53.
    Baker SM, Plug AW, Proila TA, Involvement of the mouse Mihi in DNA mismatch repair and meiotic crossing over. Nat Genet 1996;13:261–2.CrossRefGoogle Scholar
  54. 54.
    Baker SM, Bronner CE, Zhang L, Plug AW, et al. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 1995;82:303–19.CrossRefGoogle Scholar
  55. 55.
    Hales BF, Robaire B. The male-mediated developmental toxicity of cyclophosphamide. In: Mattison DR, Olshan AF, eds. Male-mediated developmental toxicity. New York: Plenum Press, 1994:105–16.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1998

Authors and Affiliations

  • Bernard Robaire
  • Barbara F. Hales

There are no affiliations available

Personalised recommendations