Mitomycin C로 유도된 염색체 이상에 대한 Hydroxyurea의 영향

Abstract

Most of the mutagens have the capacities to induce the several lesions, acting on DNA. Normally, the majority of the induced lesions are successfully repaired, only a small fractions appear as chromosomal aberrations. However, in the exposure of inhibitors of DNA synthesis, like hydroxyurea, an potentiating effects of the aberration yield is obtained. Inhibitors of DNA synthesis influencing on frequencies and types of chromosomal aberrations are depended upon types of mutagens and cells. The present study was undertaken in order to examine the potentiation by hydroxyurea in G_(2) of mitomycin C-induced chromosomal aberrations in human leukocytes. This potentiating effects by hydroxyurea were observed by compared mitotic index, frequencies and types of chromosome aberrations. In this study, a final concentration used of mitomycin C was 0.15 ug/ml, those of hydroxyurea was 5mM. The results obtained were as follows : 1. Mitotic index which group treated with mitomycin C and hydrooxyurea were significantly decreased, compared with mitomycin C or hydroxyurea treated groups. 2. Frequencies of chromosomal aberration were significantly increased in the group treated with mitomycin C and hydrooxyurea. 3. In types of chromosome aberration, groups that were treated with mitomycin C and / or hydroxyurea, induced mostly chromatid gaps. Chromatid breaks were showed dominantly in group treated with mitomycin C and hydroxyurea, than chromatid gaps. 4. The majority of chromosomal groups induced aberrations were A,B,C,D groups of chromosome. Chromatid gaps were showed significant difference between A,B,C,D groups of chromosome in group treated with both mitomycin C and hydroxyurea, and between A,B,D groups of chromosome in group treated with mitomycin C.;돌연변이 유발물질은 DNA에 작용하여 여러가지 손상(lesion)을 유발시킨다. 이러한 손상은 정상적으로 수리(repair)되나 hydroxyurea와 같은 DNA합성 저해제(inhibitors)에 노출되는 경우, 정상적인 수리작용이 저해되어 염색체 이상의 상승효과를 나타낸다고 알려져 있다. 또한 DNA합성 저해제는 돌연변이 유발물질이냐 세포의 종류에 따라 염색체 이상의 빈도와 형태에 미치는 영향이 다르다. 본 실험에서는 배양 백혈구를 이용하여 돌연변이 유발물질인 mitomycin C로 유발된 DNA손상이 수리되는 G_(2)기에 hydroxyurea를 처리한 후 세포분열계수, 염색체 이상빈도 및 형태등을 조사하여 다음과 같은 결과를 얻었다. 1. 세포분열 빈도는 mitomycin C 또는 hydroxyurea의 단독처리군에 비해 mitomycin C와 hydroxyurea의 공동처리군에서 유의하게 감소되었다. 2. 염색체 이상빈도는 mitomycin C 또는 hydroxyurea의 단독처리 군보다 mitomycin C와 hydroxyurea의 공동처리군에서 매우 유의하게 증가되었다. 3. 염색체 이상형태 중 염색분체 열극은 mitomycin C 또는 hydroxyurea의 단독처리군과 mitomycin C와 hydroxyurea의 공동처리군에서 높은 이상율을 보였고 염색분체 절단은 mitomycin C와 hydroxyurea의 공동처리군에서 가장 높은 빈도로 나타났다. 4. 염색체 이상이 유발된 염색체군은 대개 A, B, C, D군으로 나타났고, mitomycin C 단독처리군은 A, B, D군 사이에서 유의한 차이를 보였으나, mitomycin C와 hydroxyurea의 공동처리군은 A, B, C, D군 사이에서 유의한 차이를 나타냈다.