Bond S L, Singh S M
Department of Zoology, University of Western Ontario, London, Canada.
Alcohol Alcohol. 1990;25(4):385-94.
Mice (Mus musculus) from three genetic strains with variable responses to ethanol challenge (BALB/c, C57BL/6J and 129/ReJ) were used to evaluate the effect of ethanol feeding on hepatic mRNA specific to the two primary enzymes of ethanol metabolism; alcohol dehydrogenase (ADH; E.C. 1.1.1.1) and aldehyde dehydrogenase (ALDH; E.C. 1.2.1.3). Adh-1 (ADH) and Ahd-2 (ALDH) specific mRNA were evaluated on the livers of ethanol-fed mice and from their age, sex and genotype matched controls (using an isocaloric liquid diet). C57BL/6J (alcohol resistant) mice show a significant (approx. 200%) increase in ADH-1 mRNA levels after ethanol treatment, compared to their matched controls. BALB/c (alcohol sensitive) mice have approximately a 20% increase with ethanol treatment while 129/ReJ (alcohol sensitive) mice show a slight reduction in the ADH-1 specific mRNA following ethanol feeding. A strain-specific pattern is also apparent in the AHD-2 mRNA as a result of ethanol feeding in the experimental animals. C57BL/6J mice have an increase and BALB/c mice show no apparent change in the AHD-2 mRNA. 129/ReJ mice fed an ethanol diet, on the other hand, appear to have a decrease in the level of AHD-2 hepatic mRNA as compared to their matched controls. The relative mRNA levels of the two genes correlate well with the respective enzyme activity levels, but for mice on the control diet only. Ethanol feeding, which causes an apparent reduction in hepatic ADH enzyme activity in BALB/c and 129/ReJ and an apparent increase in ALDH activity in C57BL/6J (under the experimental protocols used) also alters the mRNA levels specific to the two genes. However, changes in the mRNA levels after ethanol feeding cannot be directly related to the changes seen in enzyme activity. The observed steady state level of AHD-2 mRNA and the increase in ALDH activity after ethanol feeding, which is unique to C57BL/6J mice, is expected to offer a faster clearance (metabolism) of acetaldehyde, the toxic metabolite, and may be responsible for, or contribute to, the relative resistance of this strain to ethanol.
选用对乙醇刺激有不同反应的三种基因品系的小鼠（小家鼠）（BALB/c、C57BL/6J和129/ReJ），来评估乙醇喂养对乙醇代谢的两种主要酶特异性肝mRNA的影响；乙醇脱氢酶（ADH；E.C. 1.1.1.1）和乙醛脱氢酶（ALDH；E.C. 1.2.1.3）。在乙醇喂养小鼠及其年龄、性别和基因型匹配的对照小鼠（采用等热量液体饮食）的肝脏上评估Adh-1（ADH）和Ahd-2（ALDH）特异性mRNA。与匹配的对照相比，C57BL/6J（抗酒精）小鼠在乙醇处理后ADH-1 mRNA水平显著升高（约200%）。BALB/c（酒精敏感）小鼠经乙醇处理后升高约20%，而129/ReJ（酒精敏感）小鼠在乙醇喂养后ADH-1特异性mRNA略有降低。由于实验动物乙醇喂养的结果，AHD-2 mRNA也呈现出品系特异性模式。C57BL/6J小鼠的AHD-2 mRNA增加，而BALB/c小鼠未显示明显变化。另一方面，与匹配的对照相比，喂食乙醇饮食的129/ReJ小鼠肝脏AHD-2 mRNA水平似乎降低。仅对于对照饮食的小鼠，这两个基因的相对mRNA水平与各自的酶活性水平密切相关。乙醇喂养（在所用实验方案下）导致BALB/c和129/ReJ小鼠肝脏ADH酶活性明显降低，而C57BL/6J小鼠的ALDH活性明显增加，同时也改变了这两个基因的特异性mRNA水平。然而，乙醇喂养后mRNA水平的变化与酶活性的变化没有直接关系。C57BL/6J小鼠特有的乙醇喂养后AHD-2 mRNA的观察到的稳态水平和ALDH活性的增加，预计会使有毒代谢物乙醛的清除（代谢）更快，并且可能是该品系对乙醇相对抗性的原因或促成因素。
