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-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.
Stivala
L A
LA
Istituto di Patologia Generale C. Golgi, Università di Pavia, Italy.
Pizzala
R
R
Rossi
R
R
Melli
R
R
Verri
M G
MG
Bianchi
L
L
D000818:Animals; D002470:Cell Survival; D003043:Cocarcinogenesis; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D011564:Furocoumarins / Q000528:radiation effects / Q000633:toxicity*; D006801:Humans; D008297:Male; D008730:Methoxsalen / Q000528:radiation effects / Q000633:toxicity*; D051379:Mice; D015162:Micronucleus Tests / Q000379:methods*; D009381:Neoplasms, Radiation-Induced / Q000139:chemically induced; D010777:Photochemistry; D011838:Radiation-Sensitizing Agents / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced; D014466:Ultraviolet Rays
D011564:Furocoumarins; D011838:Radiation-Sensitizing Agents; C041621:4,4',6-trimethylangelicin; D008730:Methoxsalen