Effects of beta-carotene, retinal, riboflavin, alpha-tocopherol and vitamins C and K1 on sister-chromatid exchanges induced by 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) and cyclophosphamide in human lymphocyte cultures.
The vitamins and related compounds cited in the title were investigated for their abilities to modulate sister-chromatid exchanges (SCEs) induced by Trp-P-2 or cyclophosphamide (CP) in human peripheral lymphocyte cultures in the presence of an exogenous metabolizing system from rat liver. When inducer and test substances were given simultaneously, beta-carotene, retinal and alpha-tocopherol caused a dose-dependent decrease of SCE frequencies induced by Trp-P-2 and CP. Vitamin K1, however, brought about an identical effect with Trp-P-2 only, while with CP an initial decrease of SCEs was followed by a statistically significant re-increase at higher concentrations. Vitamin C was ineffective against Trp-P-2, but caused an overall increase of SCEs induced by CP. When blood cultures were preincubated with vitamins before the addition of CP or Trp-P-2, basically identical effects were observed with beta-carotene, retinal, alpha-tocopherol, vitamin K1 and vitamin C. Riboflavin decreased SCEs induced by Trp-P-2 in all treatment schedules, although statistically confirmed minima were observed in the dose-response curves, except in post-treatment experiments. On the other hand, riboflavin only reduced SCEs induced by CP when it was preincubated with lymphocytes. When vitamins were applied in a post-treatment schedule after removal of Trp-P-2 or CP, again, basically identical results against both genotoxins were observed with beta-carotene, retinal and alpha-tocopherol with vitamin K1, however, only with respect to Trp-P-2, and with vitamin C only with respect to CP. In the post-treatment schedule, vitamin K1 caused a decrease of SCE frequencies induced by CP, and vitamin C a decrease of SCEs induced by Trp-P-2.
Department of Hygiene and Environmental Medicine, University of Mainz, Germany.
R
R
Edenharder
G
G
Kerkhoff
H
H
Dunkelberg
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002243:Carbolines / Q000633:toxicity*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000633:toxicity*; D006801:Humans; D008297:Male; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012172:Retinaldehyde / Q000494:pharmacology; D012256:Riboflavin / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects* / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D014810:Vitamin E / Q000494:pharmacology; D010837:Vitamin K 1 / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology
D000975:Antioxidants; D002243:Carbolines; D009153:Mutagens; D014815:Vitamins; D019207:beta Carotene; D014810:Vitamin E; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D010837:Vitamin K 1; D003520:Cyclophosphamide; D001205:Ascorbic Acid; D012172:Retinaldehyde; D012256:Riboflavin