PHOTOINDUCTION OF MICRONUCLEI BY 4,4',6-TRIMETHYLANGELICIN AND 8-METHOXYPSORALEN IN DIFFERENT EXPERIMENTAL-MODELS

The frequencies of micronuclei induced by treatment with 4,4',6-trimet hylangelicin (TMA) and 8-methoxypsoralen (8-MOP) have been compared in the following experimental models: (1) peripheral normochromatic eryt hrocytes (NCE) during 10 days after single p.o. administration of TMA or 8-MOP in male and female mice; (2) peripheral NCE during photocarci nogenesis by TMA or 8-MOP topically administered to female mice; (3) p rimary cultures of human skin fibroblasts treated with TMA or 8-MOP. T he frequency of micronuclei in peripheral NCE of mice (both sexes) was significantly enhanced after p.o. administration of TMA or 8-MOP. Thi s latter was more active than TMA in inducing chromosomal damage. No i ncreased 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 co ncentrations, the induction of lethal effects by TMA in the presence o f 365-nm radiation was higher than that exerted by 8-MOP. At equal sur vival, however, TMA showed practically the same activity as 8-MOP in t he induction of micronuclei. Our findings provide evidence of genotoxi city by TMA administered p.o. without irradiation and give further inf ormation about photogenotoxicity of these substances.