Submitted to: Environmental Toxicology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/19/2008
Publication Date: 12/1/2009
Publication URL: http://handle.nal.usda.gov/10113/42241
Citation: Harris, D.L., Huderson, A.C., Niaz, M.S., Ford, J.J., Archibong, A.E., Ramesh, A. 2009. Comparative Metabolism of Benzo(a)pyrene by Ovarian Microsomes of Various Species. Environmental Toxicology. 24(6):603-609. Interpretive Summary: Endocrine disruption in response to environmental toxicants is becoming an increasing concern for normal reproduction of humans and wildlife species. Ovaries from gilts in varying stages of the estrous cycle were evaluated for metabolism of benzo(a)pyrene (BAP) and compared with a number of other species. Microsomal metabolism of BAP in rodent species produced a different profile of metabolites of BAP and at a slower rate than microsomes from cow, pig, goat and sheep. These findings indicate the rodents are less informative species relative to farm mammals 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: Knowledge of the ability of the female reproductive system to metabolize polycyclic aromatic hydrocarbons (PAHs) is critical to the diagnosis and management of female infertility and for risk assessment purposes. The PAHs are a family of widespread pollutants that are released into the environment from automobile exhausts, cigarette smoke, burning of refuse, industrial emissions, and hazardous waste sites. In exposed animals, PAHs become activated to reactive metabolites that interfere with target organ function and as a consequence cause toxicity. The extent of susceptibility to PAH exposure may depend on the ability of animals to metabolize these chemicals. The present study has been undertaken to assess whether any differences exist among mammals in the metabolism of benzo(a)pyrene (BaP), a prototypical PAH compound. Microsomes isolated from the liver and ovaries of rats, mice, goats, sheep, pigs, and cows were incubated with 5 lM BaP. Postincubation, samples were extracted with ethyl acetate and analyzed for BaP/metabolites by reverse-phase HPLC with fluorescence detection. The rate of metabolism (pmol of metabolite/min/mg protein) was found to be more in liver than in ovary in all the species studied (P < 0.05). The differences in metabolite concentrations were statistically significant (P < 0.0001) among the various species in both organs studied. Multiple species comparison also revealed that the differences were statistically significant (P < 0.001) between rodents (rat and mouse) and higher mammals (ewe, sow, and cow). Even among the higher mammals, in a majority of the cases, the differences in metabolite concentrations were significantly different (P < 0.001) both in ovary and liver. The BaP metabolites identified were 4,5-diol; 7,8-diol; 9,10-diol; 3-hydroxy BaP; and 9-hydroxy BaP. The rodent microsomes produced considerably higher proportion of BaP 4,5-diol and 9,10-diol than did cow, sow, goat, and sheep. However, microsomes from higher mammals converted a greater proportion of BaP to 3-hydroxy and 9-hydroxy BaP, the detoxification products of BaP. Overall, our results revealed a great variation among species to metabolize BaP.