The combined effects of vinclozolin and procymidone do not deviate from expected additivity in vitro and in vivo

Toxicological Sciences

Volumn 71, Issue 2, 2003, Pages 251-262

  Nellemann, Christine ^a   Dalgaard, Majken ^a   Lam, Henrik Rye ^a   Vinggaard, Anne Marie ^a  

^a DANISH VETERINARY AND FOOD ADMINISTRATION   (Denmark)

Author keywords

Antiandrogen; Combination effects; Endocrine disrupters; Isobole method; Procymidone; Rats; Reporter gene assay; Vinclozolin

Indexed keywords

ANDROGEN RECEPTOR; ANTIANDROGEN; FOLLITROPIN; FUNGICIDE; LUTEINIZING HORMONE; PESTICIDE; PROCYMIDONE; SEROTONIN; TESTOSTERONE; VINCLOZOLIN;

ANIMAL EXPERIMENT; ANIMAL TISSUE; BRAIN LEVEL; CASTRATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; FOLLITROPIN BLOOD LEVEL; GENE EXPRESSION; GENITAL SYSTEM; IC 50; IN VITRO STUDY; IN VIVO STUDY; LUTEINIZING HORMONE BLOOD LEVEL; MALE; NONHUMAN; ORGAN WEIGHT; RAT; RECEPTOR BINDING; REVIEW;

ANDROGEN ANTAGONISTS; ANDROGEN-BINDING PROTEIN; ANIMALS; BICYCLO COMPOUNDS; BRAIN; CHO CELLS; CLUSTERIN; CRICETINAE; DOSE-RESPONSE RELATIONSHIP, DRUG; FOLLICLE STIMULATING HORMONE; FUNGICIDES, INDUSTRIAL; GENES, REPORTER; GENITALIA, MALE; GLYCOPROTEINS; LUTEINIZING HORMONE; MALE; MOLECULAR CHAPERONES; ORCHIECTOMY; ORGAN SIZE; OXAZOLES; RATS; RATS, WISTAR; RECEPTORS, ANDROGEN; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SEROTONIN; TRANSFECTION; UTEROGLOBIN;

ANIMALIA;

EID: 0037292159     PISSN: 10966080     EISSN: None     Source Type: Journal    
DOI: 10.1093/toxsci/71.2.251     Document Type: Review

References (40)

1. Andersen, H. R., Vinggaard, A. M., Rasmussen, T. H., Gjermandsen, I. M., and Bonefeld-Jørgensen, E. C. (2002). Effects of currently used pesticides in assays for estrogenicity, androgenicity and aromatase activity in vitro. Toxicol. Appl. Pharmacol. 179, 1-12.
2. Anton, A. H., and Sayre, D. F. (1962). A study of the factors affecting the aluminum oxidetrihydroxyindole procedure for the analysis of catecholamines. J. Pharmacol. Exp. Therap. 138, 360-375.
3. Arnold, S. F., Bergeron, J. M., Tran, D. Q., Collins, B. M., Vonier, P. M., Crews, D., Toscano, W. A., Jr., and McLachlan, J. A. (1997). Synergistic responses of steroidal estrogens in vitro (yeast) and in vivo (turtles). Biochem. Biophys. Res. Commun. 235, 336-342.
4. Ashby, J., and Lefevre, P. A. (2000). The peripubertal mate rat assay as an alternative to the Hershberger castrated male rat assay for the detection of anti-androgens, oestrogens and metabolic modulators. J. Appl. Toxicol. 20, 35-47
5. Berembaum, M. (1989). The expected effect of a combination of agents: The general solution. J. Theor. Biol. 114, 413-431.
6. Bossyns, D., Delaey, B., Rombauts, W., and Heyns, W. (1986). Influence of castration and androgen treatment on the synthesis of prostatic binding protein and the concentration of its mRNA in the rat ventral prostate. J. Steroid Biochem. 24, 661-668.
7. Gray, L. E., Jr., and Kelce, W. R. (1996). Latent effects of pesticides and toxic substances on sexual differentiation of rodents. Toxicol. Ind. Health 12, 515-531.
8. Gray, L. E., Ostby, J., Furr, J., Wolf, C. J., Lambright, C., Parks, L., Veeramachaneni, D. N., Wilson, V., Price, M., Hotchkiss, A., Orlando, E., and Guillette, L. (2001). Effects of environmental antiandrogens on reproductive development in experimental animals. Hum. Reprod Update 7, 248-264.
9. Gray, L. E., Jr., Ostby, J., and Kelce, W. R. (1994). Developmental effects of an environmental antiandrogen: The fungicide vinclozolin alters sex differentiation of the male rat. Toxicol. Appl. Pharmacol. 129, 46-52.
10. Gray, L. E., Jr., Ostby, J., Monosson, E., and Kelce, W. R. (1999). Environmental antiandrogens: Low doses of the fungicide vinclozolin alter sexual differentiation of the male rat. Toxicol. Ind. Health 15, 48-64.
11. Grimme, L. H., Faust, M., Boedeker, W., and Alterburger, R. (1996). Aquatic toxicity of chemical substances in combination: Still a matter of controversy. Human Ecol. Risk Assess. 2, 426-433.
12. Haavisto, A. M., Pettersson, K., Bergendahl, M., Perheentupa, A., Roser, J. F., and Huhtaniemi, I. (1993). A supersensitive immunofluorometric assay for rat luteinizing hormone. Endocrinology 132, 1687-1691.
13. Hellwig, J., van-Ravenzwaay, B., Mayer, M., and Gembardt, C. (2000). Pre-and postnatal oral toxicity of vinclozolin in Wistar and Long-Evans rats. Regul. Toxicol. Pharmacol. 32, 42-50.
14. Hershberger, L. G., Shipley, E., and Meyer, R. (1953). Myotrophic activity of 19-nortestosterone and other steriods determined by modified levator ani muscle method. Proc. Soc. Exp. Biol. Med. 83, 175-180.
15. Hosokawa, S., Murakami, M., Ineyama, M., Yamada, T., Koyama,Y., Okuno,Y., Yoshitake, A., Yamada, H., and Miyamoto, J. (1993a). Effects of procymidone on reproductive organs and serum gonadotropins in male rats. J. Toxicol. Sci. 18, 111-124.
16. Hosokawa, S., Murakami, M., Ineyama, M., Yamada, T., Yoshitake, A., Yamada, H., and Miyamoto, J. (1993b). The affinity of procymidone to androgen receptor in rats and mice. J. Toxicol. Sci. 18, 83-93.
17. Kelce, W. R., Lambright, C. R., Gray, L. E., Jr., and Roberts, K. P. (1997). Vinclozolin and p,p'-DDE alter androgen-dependent gene expression: In vivo confirmation of an androgen receptor-mediated mechanism. Toxicol. Appl. Pharmacol. 142, 192-200.
18. Kelce, W. R., Monosson, E., Gamcsik, M. P., Laws, S. C., and Gray, L. E., Jr. (1994). Environmental hormone disruptors: Evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. Toxicol. Appl. Pharmacol. 126, 276-285.
19. Kelce, W. R., Stone, C. R., Laws, S. C., Gray, L. E., Kemppainen, J. A., and Wilson, E. M. (1995). Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature 375, 581-585.
20. Kortenkamp, A., and Altenburger, R. (1998). Synergisms with mixtures of xenoestrogens: A reevaluation using the method of isoboles. Sci. Total Environ. 221, 59-73.
21. Kortenkamp, A., and Altenburger, R. (1999). Approaches to assessing combination effects of oestrogenic environmental pollutants. Sci. Total Environ. 233, 131-40.
22. Lam, H. R., Ladefoged, O., Ostergaard, G., Lund, S. P., and Simonsen, L. (1996). Four weeks' inhalation exposure of rats to p-cymene affects regional and synaptosomal neurochemistry. Pharmacol. Toxicol. 79, 225-230.
23. Leger, J., Montpetit, M. L., and Tenniswood, M. P. (1987). Characterization and cloning of androgen-repressed mRNAs from rat ventral prostate. Biochem. Biophys. Res. Commun. 147, 196-203.
24. McLachlan, J. A. (1997). Synergistic effect of environmental estrogens: Report withdrawn. Science 277, 462-463.
25. Moguilevsky, J. A., and Wuttke, W. (2001). Changes in the control of gonadotrophin secretion by nerutotransmitters during sexual development in rats. Exp. Clin. Endocrinol. Diabetes 109, 188-195.
26. Monosson, E., Kelce, W. R., Lambright, C., Ostby, J., and Gray, L. E., Jr. (1999). Peripubertal exposure to the antiandrogenic fungicide, vinclozolin, delays puberty, inhibits the development of androgen-dependent tissues, and alters androgen receptor function in the male rat. Toxicol. Ind. Health 15, 65-79.
27. Montpetit, M. L., Lawless, K. R., and Tenniswood, M. (1986). Androgen-repressed messages in the rat ventral prostate. Prostate 8, 25-36.
28. Nellemann, C., Vinggaard, A. M., Dalgaard, M., Hossaini, A., and Larsen, J.-J. (2001). Quantification of anti-androgen action by Lightcycler technology. Toxicology 163, 29-38.
29. Ostby, J., Kelce, W. R., Lambright, C., Wolf, C. J., Mann, P., and Gray, L. E., Jr. (1999). The fungicide procymidone alters sexual differentiation in the male rat by acting as an androgen-receptor antagonist in vivo and in vitro. Toxicol. Ind. Health 15, 80-93.
30. Payne, J., Rajapakse, N., Wilkins, M., and Kortenkamp, A. (2000). Prediction and assessment of the effects of mixtures of four xenoestrogens. Environ. Health Perspect. 108, 983-987.
31. Payne, J., Scholze, M., and Kortenkamp, A. (2001). Mixtures of four organochlorines enhance human breast cancer cell proliferation. Environ. Health Perspect. 109, 391-397.
32. Rajapakse, N., Ong, D., and Kortenkamp, A. (2001). Defining the impact of weakly estrogenic chemicals on the action of steroidal estrogens. Toxicol. Sci. 60, 296-304.
33. Rajapakse, N., Silva, E., and Kortenkamp, A. (2002). Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action. Environ. Health Perspect. 110, 917-921.
34. van Casteren, J. I. J., Schoonen, W. G. E. J., and Kloosterboer, H. J. (2000). Development of time-resolved immunofluorometric assays for rat follicle-stimulating hormone and luteinizing hormone and application on sera of cycling rats. Biol. Reprod. 62, 886-894.
35. Vercaeren, I., Vanaken, H., Devos, A., Peeters, B., Verhoeven, G., and Heyns, W. (1996). Androgens transcriptionally regulate the expression of cystatin-related protein and the C3 component of prostatic binding protein in rat ventral prostate and lacrimal gland. Endocrinology 137, 4713-4720.
36. Viard, I., Wehrli, P., Jornot, L., Bullani, R., Vechietti, J. L., Schifferli, J. A., Tschopp, J., and French, L. E. (1999). Clusterin gene expression mediates resistance to apoptotic cell death induced by heat shock and oxidative stress. J. Invest. Dermatol. 112, 290-296.
37. Vinggaard, A. M., Joergensen, E. C., and Larsen, J. C. (1999). Rapid and sensitive reporter gene assays for detection of antiandrogenic and estrogenic effects of environmental chemicals. Toxicol. Appl. Pharmacol. 155, 150-160.
38. Vinggaard, A. M., Nellemann, C., Dalgaard, M., Joergensen, E. C., and Andersen, H. R. (2002). Antiandrogenic effects in vitro and in vivo of the fungicide prochloraz. Toxicol. Sci. 69, 344-353.
39. Wilkinson, C. F., Christoph, G. R., Julien, E., Kelley, J. M., Kronenberg, J., McCarthy, J., and Reiss, R. (2000). Assessing the risks of exposures to multiple chemicals with a common mechanism of toxicity: How to cumulate? Regul. Toxicol. Pharmacol. 31, 30-43.
40. Wong, C., Kelce, W. R., Sar, M., and Wilson, E. M. (1995). Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide. J. Biol. Chem. 270, 19998-20003.