Treatment of lactating rats with PCBs induces CYP1A1 and enhances the formation of BP 7,8-dihydrodiol, the proximate carcinogen of benzo(a)pyrene.
1. Treatment of pregnant and lactating rats with a single i.p. dose of 250 mg/kg body weight produced 5-fold and 2-fold increases, respectively, in hepatic P-450 concentrations using microsomes isolated from pregnant, neonatal, lactating and foetal rats. 2. Concomitantly, 26-fold, 20-fold and 14-fold increases in neonatal, maternal and foetal ethoxyresorufin-O-deethylation (EROD), respectively were found, but only 2.5-fold increases could be determined using microsomes isolated from lactating rats. 3. The metabolism of [3H]benzo(a)pyrene was increased 9-fold and 2-fold in pregnant and foetal rats, respectively, but only 2-fold increases were measured for lactating rats. 4. Western blot analysis of microsomal proteins obtained from lactating rats showed significant CYP1A1 and CYP1A2 induction and for the same hepatic tissue 62-fold and 44-fold increases in cDNA hybridized CYP1A1 and CYP1A2 mRNA, respectively, were found. 5. Treatment of lactating rats with PCBs resulted in enhanced formation of all BP-metabolites, but the ratio of diol to total BP-metabolites was more than 3-fold greater. 6. The formation of the proximate carcinogen BP-7,8-dihydrodiol was 5-fold increased and a similar 3-fold increase in epoxide hydrolase activity was estimated for lactating rats. 7. The results of the present study indicates that lactation protects, in part, against the inductive effect of PCBs, possibly by enhanced clearance of these chemicals via lactation.
Borlakoglu
J T
JT
University of Reading, Department of Biochemistry and Physiology, U.K.
Scott
A
A
Wolf
C R
CR
Pangrekar
J
J
Sikka
H C
HC
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001564:Benzo(a)pyrene / Q000378:metabolism*; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000378:metabolism; D007774:Lactation / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D002273:Carcinogens; D004101:Dihydroxydihydrobenzopyrenes; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls