DRUG METABOLISM IN TUMOR-BEARING RATS

摘要

References(77) Cited-By(30) It has recently been recognized that the metabolism of lipid soluble compounds by liver microsomal enzymes is highly important factors for controlling the action and toxicity of various drugs (1-5). This fact is, especially, important for some drugs which should be converted to the active metabolite in vivo (5-7). Some carcinogenic and carcinostatic compounds, such as dimethylnitrosamine, 2-acethylaminofluorene, 4-nitroquinoline N-oxide and cyclophosphoramide, belong to this group (8-11). The activities of drug-metabolizing enzymes of liver microsomes are markedly altered by several factors, such as, the administrations of different kind of lipid soluble compounds and anabolic hormones, starvation, low protein diet, formaline and adrenaline stress, alloxan diabetes, hyperthyroidism, adrenalectomy, viral hepatitis and hepatectomy (1, 3, 12-20). In a preliminary work, * we observed a decrease in the metabolism of pentobarbital, meprobamate and strychnine in Walker 256 carcinosarcoma bearing male rats. However, there are clear sex difference in the alternation of activities of drug-metabolizing enzymes by the non-physiological conditions. For example, starvation, formalin and adrenaline stress, alloxan diabetes, hyperthyroidism and adrenalectomy markedly decrease the activities of most of the enzymes in male rats, while they did not significantly alter or rather increased the activities in female rats (13, 14). It would be, thus, interesting to investigate whether the decrease in the metabolism of drugs by liver microsomes of the tumor-bearing rats is only limited to male rats. Moreover, whether the activities of other drug-oxidizing enzymes, drug-reducing enzymes and electron transport systems is affected or not by tumor-bearing was investigated. Furthermore, in order to obtain some insights in the mechanism of decrease in the activities of drug-metabolizing enzymes in tumor-bearing rats, the effect of phenobarbital treatment on these enzyme activities in control rats and tumor-bearing rats was comparatively investigated.