Masuda R, Abe S, Yoshida M C, Sasaki M, Sugiyama T, Taniguchi N
Chromosome Research Unit, Faculty of Science, Hokkaido University, Sapporo, Japan.
Mutat Res. 1990 Aug;244(4):309-16. doi: 10.1016/0165-7992(90)90078-x.
LEC strain rats predisposed to hereditary hepatitis and liver cancer were examined for hepatic drug-metabolizing ability and the inducibility of chromosome damage by cyclophosphamide (CP) in somatic cells. Whereas the hepatic cytochrome P-450 contents and the activities of cytochrome P-450-catalyzed monooxygenases were lower in females than in males of both LEC and control LEA strains, male LEC rats exhibited significantly reduced cytochrome P-450 contents and monooxygenase activities compared with male LEA rats. When exposed to CP, a promutagen/procarcinogen requiring P-450-dependent metabolic activation, the frequencies of chromosome aberrations and sister-chromatid exchanges (SCEs) in bone marrow cells tended to be lower in females than in males of each strain and lower in LEC than in LEA rats of the same sex. In particular, the CP-induced SCEs were substantially lower in LEC rats. However, no such sex and strain differences were found in the SCE frequencies in regenerating hepatocytes of partially hepatectomized rats exposed to CP.
对易患遗传性肝炎和肝癌的LEC品系大鼠进行了肝脏药物代谢能力以及环磷酰胺（CP）对体细胞染色体损伤诱导性的研究。LEC品系和对照LEA品系的雌性大鼠肝脏细胞色素P-450含量以及细胞色素P-450催化的单加氧酶活性均低于雄性大鼠，而雄性LEC大鼠与雄性LEA大鼠相比，细胞色素P-450含量和单加氧酶活性显著降低。当暴露于CP（一种需要P-450依赖性代谢活化的前诱变剂/前致癌物）时，各品系雌性大鼠骨髓细胞中的染色体畸变频率和姐妹染色单体交换（SCE）频率往往低于雄性大鼠，且相同性别的LEC大鼠低于LEA大鼠。特别是，CP诱导的LEC大鼠SCE显著降低。然而，在暴露于CP的部分肝切除大鼠再生肝细胞的SCE频率中未发现此类性别和品系差异。
