Modulation of adult rat benzo(a)pyrene (BaP) metabolism and DNA adduct formation by neonatal diethylstilbestrol (DES) exposure.
This study seeks to elucidate the role of diethylstilbestrol (DES), a synthetic estrogen on benzo(a)pyrene (BaP) metabolism in the male rat reproductive tissues. Offspring of timed-pregnant Sprague-Dawley rats were neonatally treated on days 2, 4, and 6 post-partum with 1.45 micromol/kg of DES. Ten weeks after birth, the adult rats were challenged with radiolabeled benzo(a)pyrene (3H BaP) (10 micromol/kg) and the rats were sacrificed 2 h after BaP exposure. Prostrate, testis, lung, liver, urine and feces samples were collected and extracted using a mixture of H2O, MeOH and CHCl3. The extracts were analyzed by reverse phase HPLC. The concentrations of BaP organic metabolites in DES rats were lower compared to controls (vehicle-treated rats). On the other hand, concentrations of aqueous metabolites were significantly increased in DES treated animals. The toxication to detoxication ratios were significantly decreased in DES rats compared to controls. This trend is also reflected in the decreased concentrations of BaP-DNA adducts in DES rats. Collectively these results suggest that DES is capable of modulating the metabolic pathway of BaP towards detoxification thereby preventing the manifestation of toxicity.
Ramesh
Aramandla
A
Department of Pharmacology, Meharry Medical College, Nashville, TN 37208, USA. aramesh@mmc.edu
Inyang
Frank
F
Knuckles
Maurice E
ME
D000818:Animals; D000831:Animals, Newborn; D001564:Benzo(a)pyrene / Q000032:analysis / Q000378:metabolism / Q000493:pharmacokinetics* / Q000633:toxicity; D002273:Carcinogens / Q000493:pharmacokinetics* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018736:DNA Adducts / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005243:Feces / Q000737:chemistry; D005260:Female; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects / Q000378:metabolism
D002273:Carcinogens; D018736:DNA Adducts; D004968:Estrogens, Non-Steroidal; C056612:benzo(a)pyrene-DNA adduct; D001564:Benzo(a)pyrene; D004054:Diethylstilbestrol