Kazuhiro Ichikawa*, Young-Son Chung* and Hideo Utsumi*

* Faculty of Pharmaceutical Sciences, Kyushu University

+ Correspondence should be addressed to Hideo Utsumi:
(3-1-1, Maidshi, Higashi-ku, Fukuoka 812-8582 Japan)

Abstract

To evaluate the in vitro bioassay system in a liguid environment, it might be important to establish a close correlation between in vitro data and that of whole body toxicity. In order to establish a system of evaluation for in vitro bioassay, we focused on oxidative stress and investigated toxicities of organic halogenated compound using both in vitro micronucleus tests and in vivo hepatic injuries tests. The micronuclei formation of HeLa cells was induced by chlorophenols and this induction was further enhanced by the addition of S9mix. The enhancement was inhibited by scavengers of hydrogen peroxide, hydroxyl radical or superoxide radical, which indicated that micronuclei formation of HeLa cells was induced by oxidative stress caused by the metabolites of chlorophenols. Oral treatment of 2,4,6-trichlorophenol or carbon tetrachloride increased the amount of serum GOT. In vivo free radical reactions which were estimated with in vivo ESR technique were also enhanced specifically in the upper region of the abdomen, indicating that metabolites of these compounds resulted in liver injuries through oxidative stress. This study demonstrated the evaluation system of in vitro and in vivo bioassays regarding oxidative stress as caused by organic halogens. We believe the in vitro bioassay system promises to be a more valuable and reliable system, in the comparison of in vitro data with in vivo date using indices with the same leves of toxicity.

Key words: in vitro micronucleus test, electron spin resonance, whole body toxicity, organic halogenated compound