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.

Abstract

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.

• Authors: Darina Slamenová, Ivan Chalupa, Sona Robichová, Alena Gábelová, Timea Farkasová, L'ubica Hrusovská, Gabriela Bacová, Lívia Sebová, Peter Eckl, Nikolaus Bresgen, Peter Zeitheim, Peter Schneider, Ladislava Wsólová, Magdaléna Barancoková, Alena Kazimírová, Jana Navarová, Stefan Bezek
• Journal: Nutrition and cancer (Nutr Cancer) Vol. 42 Issue 1 Pg. 117-24 ( 2002) ISSN: 0163-5581 [Print] United States
• PMID: 12235643 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbazoles
• Carcinogens
• Nitrosamines
• Vitamin A
• Vitamin E
• Benzo(a)pyrene
• N-nitrosomorpholine
• 5,9-dimethyldibenzo(c,g)carbazole

Topics

• Animals
• Benzo(a)pyrene (toxicity)
• Carbazoles (toxicity)
• Carcinogens (toxicity)
• Cells, Cultured
• Chromosome Aberrations
• DNA Damage (drug effects)
• Hepatocytes (drug effects, ultrastructure)
• Male
• Micronuclei, Chromosome-Defective (drug effects)
• Nitrosamines (toxicity)
• Rats
• Rats, Wistar
• Vitamin A (administration & dosage)
• Vitamin E (administration & dosage)