Effects of β-carotene, retinal, riboflavin, α-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-tocapherol caused a dose-dependent decrease of SCE frequencies induced by Trp-P-2 and CP. Vitamin K-1, 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 K-1 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 K-1, however, only with respect to Trp-P-2, and with vitamin C only with respect to CP. In the post-treatment schedule, vitamin K-1 caused a decrease of SCE frequencies induced by CP, and vitamin C a decrease of SCEs induced by Trp-P-2. (C) 1998 Elsevier Science Ltd. All rights reserved.