Borlakoglu J T, Henderson C J, Wolf C R
University of Reading, Department of Biochemistry and Physiology, U.K.
Biochem Pharmacol. 1993 Feb 9;45(3):769-71. doi: 10.1016/0006-2952(93)90154-o.
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.
为了研究多氯联苯的泌乳期转移情况，给泌乳期大鼠低剂量注射3,4,3',4'-四氯联苯（TCB）、2,4,5,2',4',5'-六氯联苯（HCB）或TCB与HCB的混合物。作为对照，也给动物注射了Aroclor 1254。这些化学物质的泌乳期转移导致新生大鼠肝脏CYP4A血红素蛋白的诱导，所诱导的同工酶取决于所使用的化合物。在对照、TCB或HCB/TCB处理的动物中未检测到CYP4A1，但当母亲用HCB或Aroclor 1254处理时，新生大鼠中可诱导出该蛋白。就Aroclor 1254而言，效应的大小似乎取决于所使用的剂量。当母亲用Aroclor 1254而非其他所使用的试剂处理时，新生大鼠中可诱导出CYP4A2和CYP4A3。似乎TCB可诱导CYP4A基因家族的新成员。本研究提供了免疫化学证据，证明同系多氯联苯能够差异性地调节泌乳期母亲及其哺乳后代中CYP4A同工酶的表达。这些发现进一步支持了惰性亲脂性化学物质泌乳期转移所引发的潜在危害，并例证了该基因家族内基因调控的复杂性。
