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Ovarian Toxicity and Metabolism of 4-Vinylcyclohexene and Analogues in B6C3F1 Mice

Structure-Activity Study of 4-Vinylcyclohexene and Analogues
  • Julie K. Doerr
  • I. Glenn Sipes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 387)

Abstract

The industrial chemical, 4-vinylcyclohexene (VCH), is an ovarian toxicant in mice. Administration of VCH for thirty days results in depletion of ovarian follicles, including primordial follicles (Smith et al., 1990a; Hooser et al., 1994). Destruction of these non-dividing follicles produces an irreversible response that leads to the development of premature ovarian failure (Hooser et al., 1994). Since no effect in cyclicity, hormonal levels, and fertility are observed with VCH treatment until the development of ovarian failure (Hooser et al., 1994; Grizzle et al., 1994), early warning signs of ovarian toxicity are not apparent. In addition, ovarian failure is believed to be associated with the development of ovarian neoplasms (Hooser et al., 1994). An increased incidence in the occurrence of uncommon ovarian neoplasms; including mixed benign tumors, granulosa cell tumors, and granulosa cell carcinomas, is observed following chronic administration of VCH (NTP, 1986).

Keywords

Granulosa Cell Ovarian Follicle Primordial Follicle Premature Ovarian Failure Granulosa Cell Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Allen, E. (1922) The oestrus cycle in the mouse. Am. J. Anat. 30, 297–371.CrossRefGoogle Scholar
  2. Csanady, G. A., Guengerich, F. P., and Bond, J. A. (1992) Comparison of the biotransformation of 1,3-butadiene and its metabolite, butadiene monoepoxide, by hepatic and pulmonary tissues from humans, rats and mice. Carcinogenesis 13, 1143–1153.PubMedCrossRefGoogle Scholar
  3. Grizzle, T. B., George, J. D., Fail, P. A., Seely, J. C, and Heindel, J. J. (1994) Reproductive effects of 4-vinylcyclohexene in Swiss mice assessed by a continuous breeding protocol. Fundam. Appl. Toxicol. 22, 122–129.PubMedCrossRefGoogle Scholar
  4. Guengerich, F.P. (1989) Analysis and characterization of enzymes. In Principles and Methods of Toxicology (Hayes, A. W. Ed.) pp 777–814, Raven Press, Ltd., New York.Google Scholar
  5. Himmelstein, M. W., Turner, M. J., Asgharian, B., and Bond, J. A. (1994) Comparison of blood concentrations of 1,3-butadiene and butadiene epoxides in mice and rats exposed to 1,3-butadiene by inhalation. Carcinogenesis 15, 1479–1486.PubMedCrossRefGoogle Scholar
  6. Hooser, S. B., Douds, D. P., DeMerell, D. G., Hoyer, P. B., and Sipes, I. G. (1994) Long-term ovarian and gonadotropin changes in mice exposed to 4-vinylcyclohexene. Reprod. Toxicol. 8, 315–323.PubMedCrossRefGoogle Scholar
  7. Melnick, R. L., and Huff, J. (1992). 1,3-Butadiene: Toxicity and carcinogenicity in laboratory animals and in humans. Reviews of Environmental Contamination and Toxicology 124, 111–144.PubMedCrossRefGoogle Scholar
  8. National Toxicology Program (1986) Toxicology and carcinogenesis studies of 4-vinylcyclohexene in F344/N rats and B6C3F1 mice (gavage studies). U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC, Technical Report No. 303.Google Scholar
  9. National Toxicology Program (1989) Toxicology and carcinogenesis studies of 4-vinylcyclohexene diepoxide in F344/N rats and B6C3F1 mice (dermal studies). U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Research Triangle Park, NC, Technical Report No. 362.Google Scholar
  10. Oesch, F., Kaubisch, N., Jerina, D. M., and Daly, J. W. (1971) Hepatic epoxide hydrase: Structure-activity relationships for substrates and inhibitors. Biochemistry 10, 4858–4866.PubMedCrossRefGoogle Scholar
  11. Omura, T., and Sato, R. (1964) The carbon monoxide-binding pigment of liver microsomes. J. Biol. Chem. 239, 2370–2385.PubMedGoogle Scholar
  12. Pedersen, T., and Peters, H. (1968) Proposal for a classification of oocytes and follicles in the mouse ovary. J. Reprod. Fert. 17,555–557.CrossRefGoogle Scholar
  13. Smith, B. J., Mattison, D. R., and Sipes, I. G. (1990a) The role of epoxidation in 4-vinylcyclohexene-induced ovarian toxicity. Toxicol. Appl. Pharmacol. 105, 372–381.PubMedCrossRefGoogle Scholar
  14. Smith, B. J., Carter, D. E., and Sipes, I. G. (1990b) Comparison of the disposition and in vitro metabolism of 4-vinylcyclohexene in the female mouse and rat. Toxicol. Appl. Pharmacol 105, 364–371.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Julie K. Doerr
    • 1
  • I. Glenn Sipes
    • 1
  1. 1.Department of Pharmacology and Toxicology College of PharmacyUniversity of ArizonaTucsonUSA

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