Lum P Y, Walker S, Ioannides C
Toxicology. 1985 Jun 28;35(4):307-17. doi: 10.1016/0300-483x(85)90064-2.
Benzphetamine N-demethylase (cytochrome P-450) and ethoxyresorufin O-deethylase activities (cytochrome P-448) were determined in the growing neonate and foetus of control and 3-methylcholanthrene-pretreated rats. Ethoxyresorufin O-deethylase activity was highest in the 1-2-week-old animals and then decreased with age. The inducibility of this activity by 3-methylcholanthrene was low in the young animals, but increased with age. In contrast, benzphetamine N-demethylase activity in the control animals was low at birth and increased with age, and was not induced by 3-methylcholanthrene. In the foetal liver, ethoxyresorufin O-deethylase was the only activity present at higher levels than in the maternal liver. Transplacental administration of 3-methylcholanthrene failed to induce the foetal activities while the maternal liver showed the expected response. These observations demonstrate that cytochrome P-448 may be a predominant hepatic form in the foetus and neonate but cytochrome P-450 becomes a major form as the animal grows. The implications of these findings in chemical toxicity are discussed.
在对照组和经3-甲基胆蒽预处理的大鼠的新生幼崽和胎儿中，测定了苄非他明N-脱甲基酶（细胞色素P-450）和乙氧试卤灵O-脱乙基酶活性（细胞色素P-448）。乙氧试卤灵O-脱乙基酶活性在1至2周龄的动物中最高，然后随年龄增长而降低。这种活性在幼龄动物中对3-甲基胆蒽的诱导性较低，但随年龄增长而增加。相比之下，对照组动物中的苄非他明N-脱甲基酶活性在出生时较低，并随年龄增长而增加，且不受3-甲基胆蒽诱导。在胎儿肝脏中，乙氧试卤灵O-脱乙基酶是唯一比母体肝脏中水平更高的活性。经胎盘给予3-甲基胆蒽未能诱导胎儿的活性，而母体肝脏显示出预期的反应。这些观察结果表明，细胞色素P-448可能是胎儿和新生儿肝脏中的主要形式，但随着动物生长，细胞色素P-450成为主要形式。讨论了这些发现对化学毒性的影响。
