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Title: Species-specific testicular and hepatic microsomal metabolism of benzo(a)pyrene, an ubiquitous toxicant and endocrine disruptor

Author
item SMITH, TENE - FISK UNIV, NASHVILLE TN
item MERRY, SHAYLA - FISK UNIV, NASHVILLE TN
item HARRIS, DEACQUNITA - MEHARRY MED COLLEGE, TN
item Ford, Johny
item IKE, JUSTUS - FISK UNIV, NASHVILLE TN
item ARCHIBONG, ANTHONY - MEHARRY MED COLLEGE, TN
item RAMESH, ARAMANDLA - MEHARRY MED COLLEGE, TN

Submitted to: Toxicology In Vitro
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/8/2007
Publication Date: 6/1/2007
Citation: Smith, T.L., Merry, S.T., Harris, D.L., Ford, J.J., Ike, J., Archibong, A.E., Ramesh, A. 2007. (Brief Communication) Species-specific testicular and hepatic microsomal metabolism of benzo(a)pyrene, an ubiquitous toxicant and endocrine disruptor. Toxicology In Vitro. 21(4):753-758.

Interpretive Summary: Endocrine disruption in response to environmental toxicants is becoming an increasing concern for normal reproduction of humans and wildlife species. Boars were selected to include in an evaluation of testicular and hepatic metabolism of benzo(a)pyrene (BaP) across a number of species due to the large quantity of interstitial tissue within the testes of boars. Microsomal metabolism of BaP in rodent species produced a different profile of metabolites of BaP than microsomes from boar, goat, ram and monkey. These findings indicate the rodents are less informative species relative to primates for evaluation of the metabolism of polycyclic aromatic hydrocarbons such as BaP. The findings will be useful in the design of subsequent studies and will aid in the establishment of protocols by regulatory agencies.

Technical Abstract: Information on the metabolism of the environmental toxicant, benzo(a)pyrene (BaP) in the male reproductive system is crucial for understanding BaP-induced infertility. Microsomes were isolated from the liver and testes of rat, mouse, hamster, ram, boar, bull, and monkey and incubated with BaP. Post-incubation, samples were extracted with ethyl acetate and analyzed for BaP/metabolites by reverse-phase HPLC with fluorescence detection. A great variation among species to metabolize BaP was observed. The rodent testicular microsomes produced higher proportions of BaP 4,5-diol and 9, 10-diol than did boar, ram, bull, and monkey. On the other hand, hepatic microsomes from higher mammals converted a greater proportion of BaP to 3-hydroxy and 9-hydroxy BaP, the detoxification products of BaP. Given the ability of BaP 7-8-diol 9, 10-epoxide, 3-, and 9-hydroxy BaP to bind with DNA and form adducts, there is a likelihood of risk arising from the accumulation of BaP metabolites in testicular tissues. These metabolites may interfere with the formation and function of gametes, eventually contributing to infertility.