Finlayson M J, Bellward G D
Drug Metab Dispos. 1982 Jan-Feb;10(1):74-6.
I-alpha-Acetylmethadol (LAAM) was administered via the drinking water to female Wistar rats throughout pregnancy and lactation. Controls were pair-fed and watered. After weaning, pups received lab chow and water ad lib. until maturity. The apparent KM and Vmax were determined for benzo[a]pyrene hydroxylase (BPH), aminopyrine N-demethylase (AP), ethylmorphine N-demethylase (ET) and aniline hydroxylase (AN) from the hepatic microsomal fraction of the mature male and female offspring. The dose of LAAM administered was low enough to produce no symptomatology. In the adult male, pre- and neonatal exposure to LAAM resulted in decreases in KM for AP and Vmax for AN, and increase in the KM and Vmax for BPH. For the female, LAAM produced an increase in KM for AP and a decrease in Vmax for ET and BPH. That is, long-term changes occurred in the enzyme parameters measured; the direction of the changes were sex- and substrate-dependent.
在整个怀孕和哺乳期，通过饮用水向雌性Wistar大鼠施用α-乙酰美沙多（LAAM）。对照组采用配对喂食和饮水方式。断奶后，幼崽随意进食实验室饲料和饮水，直至成熟。测定了成熟雄性和雌性后代肝脏微粒体部分中苯并[a]芘羟化酶（BPH）、氨基比林N-脱甲基酶（AP）、乙基吗啡N-脱甲基酶（ET）和苯胺羟化酶（AN）的表观米氏常数（KM）和最大反应速度（Vmax）。所施用的LAAM剂量足够低，未产生任何症状。在成年雄性中，产前和新生儿期接触LAAM导致AP的KM降低、AN的Vmax降低，以及BPH的KM和Vmax增加。对于雌性，LAAM导致AP的KM增加、ET和BPH的Vmax降低。也就是说，所测量的酶参数发生了长期变化；变化的方向取决于性别和底物。
