Borlakoglu J T, Clarke S, Huang S W, Dils R R, Haegele K D, Gibson G G
Marion Merrell Dow Research Institute, Strasbourg, France.
Biochem Pharmacol. 1992 Jan 22;43(2):153-7. doi: 10.1016/0006-2952(92)90272-k.
On the first day of lactation, material rats were treated with a single low dose of 5 mg/kg body weight of 3,3',4,4'-tetrachlorobiphenyl (TCB) or 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) or with a combination of both congeners. Lactational transfer of these polychlorinated biphenyls (PCBs) was found in neonates and significant increases in microsomal cytochrome P450, cytochrome b5 and in glutathione-S-transferase activity were observed. Treatment with HCB did not increase neonatal ethoxyresorufin-O-de-ethylation (EROD) activities whereas a more than 26-fold increase in EROD activity was noted in response to exposure to TCB. However, EROD activities were increased more than 65-fold in response to the combined exposure to TCB and HCB. Exposure via milk to TCB caused a significant reduction in the N-demethylation of aminopyrine, but the combined exposure to TCB and HCB produced a significant reduction in the N-demethylation of dimethylnitrosamine. Lactational transfer of either TCB or HCB reduced marginally peroxisomal enzyme activities; however, exposure to a combination of TCB and HCB resulted in the highly significant reduction in KCN-insensitive palmitoyl-CoA oxidation and acetyl-CoA oxidation. Contrary to the reduction of these enzyme activities, the specific concentrations of CYP4A1 were significantly increased when neonates were exposed to either TCB or HCB. The largest induction, however, was observed in response to the combined exposure to both PCBs. Evidence is presented to suggest an induction of CYP4A1 which may be independent of the molecular substitution pattern of the two PCBs used in our studies but on a possible mode of synergistic interaction.
在哺乳期第一天，给母鼠单次低剂量腹腔注射5毫克/千克体重的3,3',4,4'-四氯联苯（TCB）或2,2',4,4',5,5'-六氯联苯（HCB），或两种同系物的组合。在新生鼠中发现了这些多氯联苯（PCBs）的乳汁转移，并观察到微粒体细胞色素P450、细胞色素b5和谷胱甘肽-S-转移酶活性显著增加。用HCB处理并未增加新生鼠的乙氧基异吩恶唑酮-O-脱乙基酶（EROD）活性，而暴露于TCB后EROD活性增加了26倍以上。然而，同时暴露于TCB和HCB时，EROD活性增加了65倍以上。通过乳汁暴露于TCB会导致氨基比林的N-脱甲基化显著降低，但同时暴露于TCB和HCB会使二甲基亚硝胺的N-脱甲基化显著降低。单独暴露于TCB或HCB会使过氧化物酶体酶活性略有降低；然而，同时暴露于TCB和HCB会导致对氰化钾不敏感的棕榈酰辅酶A氧化和乙酰辅酶A氧化显著降低。与这些酶活性的降低相反，当新生鼠暴露于TCB或HCB时，CYP4A1的特定浓度显著增加。然而，在同时暴露于两种多氯联苯时观察到最大的诱导作用。有证据表明CYP4A1的诱导可能与我们研究中使用的两种多氯联苯的分子取代模式无关，而是与一种可能的协同相互作用模式有关。
