3-methylcholanthrene (3-MC), phenobarbital (Pb), ethyl alcohol, catechol을 단일물질로 또는 이들의 혼합물로 Sprague Dawley계 흰쥐 (male, 160~180gr)에 각각 5일동안 복강주사한후 간장, 허파, 비장의 aryl hydrocarbon hydroxylase (AHHase, EC 1.14. 14. 1) 수준의 비교와 3-MC와 Pb에 의해 유도된 간의 Cytochrome P-450 (P-450)의 주된 동위효소를 측정하여 다음과 같은 결과를 얻었다. 3-MC, 3-MC+ethyl alcohol 또는 Pb 처리의 경우 간장에서 AHHase 유도가 가장 증가되었으며 그밖의 장기에서는 대조구와 큰 차이를 보이지 않았다. 3-MC+catechol과 3-MC+ethyl alcohol의 투여는 3-MC와 달리 비장에서 괄목할만한 유도수준을 나타냈으며 특히 3-MC+catechol의 경우 비장의 AHHase 유도물질로서 좀더 연구할 가치가 있다고 생각된다. 한편 3-MC 또는 Pb 쳐리에 의해 유도된 간장에서의 P-450 함량과 AHHase 활성도의 관계는 P-450이 3-MC보다 Pb에 의해 더 많이 유도되었으나 AHHase 활성도는 낮았다. 이것은 Pb로 유도된 간장의 P-450은 최적기질이 본 연구에 사용된 benzo(a)pyrene이 아니고 benzphetamine이기 때 문이며 3-MC 또는 Pb로 유도된 P-450 동위효소의 농도분포가 각각 다른 것을 시사하고 있다. 이에 따라 monoclonal antibodies에 의해 동위효소 각각에 대한 유도정도를 측정한 결과 Pb에 의한 P-450-b는 약 30%, 3-MC의 P-450-c는 약 70%d의 동위효소를 확인할 수 있었다. 그러나 benzphetamine demethylase 측정의 경우 P-450-b의 수준은 보다 증가될 것으로 예상된다.
The induction levels of microsomal aryl hydrocarbon hydroxylase (AHHase, EC 1.14. 14.1) in tissues of Sprague-Dawley rats (male, 160-180g) were investigated after i.p. administration with 3-methylcholanthrene (3-MC), phenobarbital (Pb), catechol and ethyl alcohol, or these mixtures. 3-MC, 3-MC+ethyl alcohol or Pb treatment significantly induced AHHase level in all the groups tested, whereas AHHase activities by treatment of ethyl alcohol or catechol had not reached that of 3-MC or Pb in liver. When rats were treated with mixture of 3-MC and catechol, kidney was the tissue most sensitive to induction of AHHase in all cases. Pb-induced P-450 content was greatly higher than that of 3-MC, but apparent AHHase induction was observed in the livers of rats treated 3-MC as compared to that of the corresponding Pb. There was because the patterns of induction of AHHase activities by Pb or 3-MC were not only very different, but induction levels of P-450 isozymes (P-450-a, P-450-b, P-450-c, P-450-d) from liver were also different. The Pb-monoclonal antibody inhibited about 30% of the AHHase activities of Pb-induced liver microsome at a concentration of $200{mu}g$ ascites fluid protein per reaction mixture (ml). The liver microsome from 3-MC-treated rats also were inhibited about 70% of the AHHase activity by 3-MC-monoclonal antibody. These results demonstrate that the high induction of 30% of P-450-b and 70% of P-450-c in total P-450s of rat liver microsomes by Pb or 3-MC treatment, respectively.
