Lactational transfer of 2,4,5,2',4',5'-hexachlorobiphenyl but not 3,4,3',4'-tetrachlorobiphenyl, induces neonatal CYP4A1.
In order to study the lactational transfer of polychlorinated biphenyls, lactating rats were treated with a low dose of either 3,4,3',4'-tetrachlorobiphenyl (TCB), 2,4,5,2',4',5'-hexachlorobiphenyl (HCB) or a combination of TCB and HCB. For comparison, animals were also treated with Aroclor 1254, Lactational transfer of these chemicals resulted in the induction of neonatal hepatic CYP4A haemoproteins, the isozymes induced being dependent on the compound used. CYP4A1 was not detected in control, TCB or HCB/TCB-treated animals, but was induced in neonates when mothers were treated with HCB or Aroclor 1254. In the case of Aroclor 1254, the magnitude of the effect appeared to be dependent on the dose used. CYP4A2 and CYP4A3 were induced in the neonates when mothers were treated with Aroclor 1254 but not with the other agents used. It appears that TCB induces novel members of the CYP4A gene family. The present study provides immunochemical evidence for the ability of congeneric polychlorinated biphenyls to modulate differentially the expression of CYP4A isozymes in lactating mothers and their suckling offspring. These findings further support the potential hazards induced by lactational transfer of inert lipophilic chemicals and exemplify the complexity of the regulation of genes within this gene family.
Borlakoglu
J T
JT
University of Reading, Department of Biochemistry and Physiology, U.K.
Henderson
C J
CJ
Wolf
C R
CR
D000818:Animals; D000831:Animals, Newborn; D001140:Aroclors / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis*; D007774:Lactation; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001140:Aroclors; D007527:Isoenzymes; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; C028451:3,4,3',4'-tetrachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl