간세포암 환자에서 bleomycin에 대한 염색체 감수성의 의의

Abstract

Backgrounds/Aims: There are interindividual differences, genetically determined, in susceptibility to ."ancer and such variable susceptibility may reflect individual variation in DNA repair capability. A cytogenetic assay, so-called mutagen sensitivity assay, has been developed in which in vitro bleomycin-induced chromosome breaks provide indirect measure of such repair. By assessing muta- gen sensitivity in patients with chronic liver disease(CLD) and hepatocellular carcinoma(HCC), we explored the possibility of interindividual differences in chrornosomal susceptibility to mutagen and evaluated the significance of mutagen sensitivity in patients with HCC. Methods: Lymphocytes from 14 patients with CLD and 21 patients with HCC were cultured in vitro and challenged with bleornycin. Chrornosomal damage was quantified by scoring chromatid breaks of 100 metaphase cells. Results: Chromosomal sensitivity to bleomycin varied interindividua]ly in both patients with CLD and HCC, the number of bleomycin-induced chromatid breaks per cell(b/c) ranging from 0.2 to 0.6. The mean b/c value showed no significant difference between the two groups(0.37+0.06 in CLD vs 0.43+0.07 in HCC). However, the distributional profiles of b/c differed significantly between the two groups, the frequency of subjects with a b/c value of >0.4 being significantly higher in HCC patients than CLD patients(61.8% vs 28.5%, p0.05). Bleomycin sensitivity in HCC patients was influenced by patients age an<I family history of the disease(p0.05), but not by alcohol or smoking history and sex. The patients of HCC with young age onset or with a positive family history responded with a relatively higher degree of b/c value. Conclusions: We could observe interindividual differences in sensitivity to bleomycin-induced chromosomal damage and that bleomycin-sensitive subjects were more common in HCC patients than CLD patients, especially in those with young age or who had a family history of HCC. These findings suggest that bleomycin-induced chromosomal sensitivity may serve as an indicator of genetic susceptibility to the development of HCC.