Effect of dietary intake of vitamin A or E on the level of DNA damage, chromosomal aberrations, and micronuclei induced in freshly isolated rat hepatocytes by different carcinogens.
Hepatocytes freshly isolated from male Wistar rats fed a common diet or a vitamin A- or vitamin E-supplemented diet (each for 21, 28, or 41 days) were assayed for sensitivity to DNA breakage and cytogenetic changes induced by carcinogens. Different indirectly acting carcinogens were assayed. N-nitrosomorpholine (NMOR) was the only agent that induced DNA breaks, chromosomal aberrations, and micronuclei in all experiments. Benzo[a]pyrene (B[a]p) and dimethyldibenzo [c,g]carbazole (diMeDBC) induced only DNA breaks in all experiments. Occasionally, B[a]P induced chromosomal aberrations and micronuclei, and diMeDBC induced micronuclei, but not chromosomal aberrations. These results demonstrated that the tested carcinogens assayed at concentrations highly effective in a hypoxanthine phosphoribosyltransferase/V79 system significantly increased DNA damage, while cytogenetic changes were less frequent. In hepatocytes from rats fed vitamin A, a reduction in the severity of all three end points was observed after NMOR treatment. After B[a]P treatment, we found a reduction in DNA breaks and chromosomal aberrations; after treatment with diMeDBC, we observed a reduction in DNA breaks. Treatment with vitamin E was less effective: it reduced DNA strand breaks induced by B[a]P and partially reduced those induced by diMeDBC and NMOR and the level of micronuclei induced by NMOR and B[a]P. Both vitamins reduced the level of DNA strand breaks induced by the oxidative effect of a visible light-excited photosensitizer.
Slamenová
Darina
D
Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic.
Chalupa
Ivan
I
Robichová
Sona
S
Gábelová
Alena
A
Farkasová
Timea
T
Hrusovská
L'ubica
L
Bacová
Gabriela
G
Sebová
Lívia
L
Eckl
Peter
P
Bresgen
Nikolaus
N
Zeitheim
Peter
P
Schneider
Peter
P
Wsólová
Ladislava
L
Barancoková
Magdaléna
M
Kazimírová
Alena
A
Navarová
Jana
J
Bezek
Stefan
S
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002227:Carbazoles / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004249:DNA Damage / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D009602:Nitrosamines / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D014801:Vitamin A / Q000008:administration & dosage*; D014810:Vitamin E / Q000008:administration & dosage*
D002227:Carbazoles; D002273:Carcinogens; D009602:Nitrosamines; D014801:Vitamin A; D014810:Vitamin E; D001564:Benzo(a)pyrene; C002741:N-nitrosomorpholine; C039387:5,9-dimethyldibenzo(c,g)carbazole