In vitro induction of cytochrome P-450 associated monooxygenases by pehenobarbiatal(PB) and 3-methylcholanthrene(3-MC) was investigated in primary cultures of adult rat hepatocytes. 3-MC and PB were treated 24 hr often plating of hepatocytes and four monooxygenases activities were measured. 7-Ethoxycoumarin 0-deethylase and aryl hydrocarbon hydroxylase activities were increased to higher level than initial value by MC but, by PB, were increased to similar level of initial value. Biphenyl 4-hydroxylase and aminopyrine N-demethylase activities did not increased to initial level but maintenance effects could be seen. Induction pattern of PB and 3-MC was characteric. DNA repair synthesis was measured by determining $^3H$-thymidine incorporation into DNA for aflatoxin $B_1$ treated hepatocytes. Unscheduled DNA synthesis experiments were performed for untreated, PB and 3-MC treated hepatocytes. At the lower concentration of $AFB_1$, the same extent of unscheduled DNA synthesis was shown in untreated and inducer treated hepatocytes. However, at the higher concentration of $AFB_1$, in vitro administration of inducers enhanced unscheduled DNA synthesis induced by $AFB_1$. These results showed that this system may have application in the investigation of hepartocarcinogenesis by chemicals in vitro.
본 연구에서는 배양 중에 급격히 감소하는 약물 대사 능력을 증가시키기 위하여 inducer 를 배양액에 직접 첨가 하였다. 약물 대사 능력은 7-ethoxycoumarin 0-deethylase, aryl hydrocarbon hydroxylase, biphenyl 4-hydroxylase, aminopyrine N-demethylase 의 네가지로 측정하였다. 이 enzyme 들은 inducer 가 첨가 되지 않았을 때는 급격히 감소하였으나, inducer 첨가시에는 각각 특징적으로 증가하는 양상을 보여주었다. 위와같이 인위적으로 약물 대사 능력을 향상시킨 간세포가 독성학 연구에 유용한 지를 알아보기 위해, Aflatoxin B 에 의해 야기되는 비주기성 DNA 합성을 측정하였다. Aflatoxin B 의 농도가 낮을 때는 inducer 를 처리한 군과 처리하지 않은 군에서의 비주기성 DNA 합성 정도가 비슷하였으나, Aflatoxin B 의 농도가 높을 때는 inducer 를 처리한 군에서 더 높은 정도의 비주기성 DNA 합성이 일어났다.
