Enhancement of Chromosome Aberrations in Lymphocytes of Mice after in Vivo Exposure to Chemicals and in Vitro Challenge with Bleomycin

MNNG 또는 Benzo(a)pyrene 유도 염색체 이상에 미치는 Bleomycin의 효과

Exposure to environmental toxicants can cause cellular problems including the interference of DNA repair processes which may lead to the development of cancer. The existence of toxicant-induced DNA repair abnormality was investigated using mice exposed in vivo to genotoxic chemicals and then challenging their exposed lymphocytes in vitro with bleomycin. The repair of bleomycin-induced DNA damage as estimated by the frequency of chromosome aberrations was determined. Our data indicates that the observed aberration frequencies after in vivo exposure to N-methyl-N'-nitro-N-nitnsoguanidine (MNNG) and in vitro challenge with bleomycin are consistently higher than expected. The enhanced response is not due to the induction of chromosome damage by 25 or 50 mg/kg MNNG since the chemical did not cause chromosome aberrations in lymphocytes of these mice. The observed response after the combined exposure to benzo[a]pyrene (BP) and bleomycin was significantly lower than expected with low in vivo doses of BP (50 mg/kg) and then significantly higher than expected with the high doses (200 mg/kg). We interpret our data to indicate that in vivo exposure to genotoxic agents can cause abnormal DNA repair activities. The response is, however, independent of the clastogenic activities of the inducing chemicals, but dependent upon the inducing agents and on the exposure doses.

환경독성물질에 의한 폭로는 세포내 DNA의 수복과정에 영향을 미쳐 돌연변이나 암을 유발할 수 있다. 독성물질에 의해 유도된 DNA의 비정상 수복효과를 판단하기 위하여.in vivo에서 MNNG 또는 Benzo(a)pyrene을 투여하고 in vitro에서 Bleomycin을 처리하여 나타나는 염색체이상효과를 관찰하였다. 실험결과, MNNG를 투여 후 Bleomycin을 처리하였을 때 염색체이상의 상승효과가 나타났다. 한편, Benzo(a)pyrene 투여 후 Bleomycin을 처리하였을 패는 높은 농도에서 염색체이상의 상승효과가 나타났다. 이같은 결과는 MNNG나 Benzo(a)pyrene 같은 유전독성물질들이 in vivo에서 세포내 비정상 DNA수복을 일으킬 수 있으며, 이러한 작용은 관련 유전독성물질의 염색체손상성에 무관하며 투여용량에 의존되는 것으로 판단된다.