EFFECTS OF BETA-CAROTENE, RETINAL, RIBOFLAVIN, ALPHA-TOCOPHEROL AND VITAMIN-C AND VITAMIN-K-1 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 investigate d for their abilities to modulate sister-chromatid exchanges (SCEs) in duced by Trp-P-2 or cyclophosphamide (CP) in human peripheral lymphocy te cultures in the presence of an exogenous metabolizing system from r at liver. When inducer and test substances were given simultaneously, beta-carotene, retinal and alpha-tocapherol caused a dose-dependent de crease of SCE frequencies induced by Trp-P-2 and CP. Vitamin K-1, howe ver, brought about an identical effect with Trp-P-2 only, while with C P an initial decrease of SCEs was followed by a statistically signific ant re-increase at higher concentrations. Vitamin C was ineffective ag ainst Trp-P-2, but caused an overall increase of SCEs induced by CP. W hen 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. Ribof lavin decreased SCEs induced by Trp-P-2 in all treatment schedules, al though statistically confirmed minima were observed in the dose-respon se curves, except in post-treatment experiments. On the other hand, ri boflavin 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 aga inst both genotoxins were observed with beta-carotene, retinal and alp ha-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 sch edule, 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 Elsevie r Science Ltd. All rights reserved.