Lucas D, Ménez J F, Berthou F, Cauvin J M, Deitrich R A
Faculté de Médecine, Laboratoire de Biochimie, Brest, France.
Alcohol Clin Exp Res. 1992 Oct;16(5):916-21. doi: 10.1111/j.1530-0277.1992.tb01893.x.
High and low alcohol sensitivity (HAS and LAS) rats have been selected for their differences in ethanol-induced sleep time. Liver monooxygenase activities were studied in HAS and LAS rats before and after treatments with known inducers such as chronic ethanol, pyrazole, 3-methylcholanthrene (3-MC) and phenobarbital (PB) to determine whether the selection procedure also selected for differences in the cytochrome P-450 (P-450) inducibility. This previously has been shown with long sleep (LS) and short sleep (SS) mice, which were selected using a similar criterion. 3-MC and PB, in conjunction with chronic ethanol treatment, were used in order to evaluate the interactions of ethanol with these inducers. Prior to treatment, total P-450 content was slightly lower in LAS than in HAS rats. However, both lines displayed the same microsomal monooxygenase activities related to different P-450 isozymes. This was demonstrated by ethoxyresorufin deethylation (EROD) for cytochrome P-450 1A1 (CYP1A1), acetanilide hydroxylation (ACET) for CYP1A2, pentoxyresorufin dealkylation (PROD) for CYP2B, 1-butanol oxidation (BUTAN) and N-nitrosodimethylamine demethylation (NDMA) for CYP2E1. After the different treatments, HAS rats did not differ from LAS rats in their CYP2E1 inducibility. However, pyrazole, PB and 3-MC treatment led to differences in CYP1A and CYP2B monooxygenase activities between the two lines. The enhancement of PROD by pyrazole treatment was less prominent in LAS (1.7-fold of the control value) than in HAS rats (3.8-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
高酒精敏感性和低酒精敏感性（HAS和LAS）大鼠因其乙醇诱导睡眠时间的差异而被挑选出来。在用已知诱导剂如慢性乙醇、吡唑、3-甲基胆蒽（3-MC）和苯巴比妥（PB）处理前后，研究了HAS和LAS大鼠肝脏单加氧酶活性，以确定这种挑选过程是否也选择了细胞色素P-450（P-450）诱导性方面的差异。此前，使用类似标准挑选出的长睡眠（LS）和短睡眠（SS）小鼠也显示出这种情况。使用3-MC和PB并结合慢性乙醇处理，以评估乙醇与这些诱导剂的相互作用。处理前，LAS大鼠的总P-450含量略低于HAS大鼠。然而，两条品系在与不同P-450同工酶相关的微粒体单加氧酶活性方面表现相同。这通过细胞色素P-450 1A1（CYP1A1）的乙氧基试卤灵脱乙基作用（EROD）、CYP1A2的乙酰苯胺羟基化作用（ACET）、CYP2B的戊氧基试卤灵脱烷基作用（PROD）、CYP2E1的1-丁醇氧化作用（BUTAN）和N-亚硝基二甲胺脱甲基作用（NDMA）得到证实。经过不同处理后，HAS大鼠和LAS大鼠在CYP2E1诱导性方面没有差异。然而，吡唑、PB和3-MC处理导致两条品系在CYP1A和CYP2B单加氧酶活性方面存在差异。吡唑处理对PROD的增强作用在LAS大鼠（为对照值的1.7倍）中不如在HAS大鼠中（为对照值的3.8倍）明显。（摘要截短至250字）
