Stivala L A, Pizzala R, Rossi R, Melli R, Verri M G, Bianchi L
Istituto di Patologia Generale C. Golgi, Università di Pavia, Italy.
Mutat Res. 1995 Mar;327(1-2):227-36. doi: 10.1016/0027-5107(94)00193-9.
The frequencies of micronuclei induced by treatment with 4,4',6-trimethylangelicin (TMA) and 8-methoxypsoralen (8-MOP) have been compared in the following experimental models: (1) peripheral normochromatic erythrocytes (NCE) during 10 days after single p.o. administration of TMA or 8-MOP in male and female mice; (2) peripheral NCE during photocarcinogenesis by TMA or 8-MOP topically administered to female mice; (3) primary cultures of human skin fibroblasts treated with TMA or 8-MOP. The frequency of micronuclei in peripheral NCE of mice (both sexes) was significantly enhanced after p.o. administration of TMA or 8-MOP. This latter was more active than TMA in inducing chromosomal damage. No increased frequencies of micronuclei in peripheral NCE were detected in mice subjected to TMA or 8-MOP photocarcinogenic treatment, even when malignancies developed. In human fibroblast cultures, at equimolar concentrations, the induction of lethal effects by TMA in the presence of 365-nm radiation was higher than that exerted by 8-MOP. At equal survival, however, TMA showed practically the same activity as 8-MOP in the induction of micronuclei. Our findings provide evidence of genotoxicity by TMA administered p.o. without irradiation and give further information about photogenotoxicity of these substances.
在以下实验模型中比较了4,4',6-三甲基补骨脂素（TMA）和8-甲氧基补骨脂素（8-MOP）诱导微核的频率：（1）雄性和雌性小鼠单次口服TMA或8-MOP后10天内的外周正染红细胞（NCE）；（2）对雌性小鼠局部施用TMA或8-MOP进行光致癌过程中的外周NCE；（3）用TMA或8-MOP处理的人皮肤成纤维细胞原代培养物。口服TMA或8-MOP后，小鼠（两性）外周NCE中的微核频率显著增加。后者在诱导染色体损伤方面比TMA更活跃。即使发生了恶性肿瘤，接受TMA或8-MOP光致癌处理的小鼠外周NCE中的微核频率也未检测到增加。在人成纤维细胞培养物中，在等摩尔浓度下，在365纳米辐射存在下TMA诱导的致死效应高于8-MOP。然而，在相同存活率下，TMA在诱导微核方面与8-MOP表现出几乎相同的活性。我们的研究结果提供了口服TMA（未照射）具有遗传毒性的证据，并给出了这些物质光遗传毒性的进一步信息。
