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Inhibition of cyclophosphamide and mitomycin c-induced sister chromatid exchanges in mice by vitamin c.

Krishna-G; Nath-J; Ong-T
Cancer Res 1986 Jun; 46(6):2670-2674
The effect of ascorbic-acid (50817) on the induction of sister chromatid exchanges (SCEs) by cyclophosphamide (50180) (CPA) and mitomycin-C (50077) (MMC) was studied in bone marrow and spleen cells of mice under in-vivo and in-vivo/in-vitro conditions. Male CD-1-mice were given intraperitoneal injections of 40mg/kg CPA, 2.5mg/kg MMC or vehicle, followed immediately by injections of 0, 1.67, 3.34, or 6.68 grams per kilogram (g/kg) ascorbic-acid. Under in-vivo conditions, animals were pretreated with 5-bromo-2'- deoxyuridine (BrdUrd) and were administered colchicine prior to sacrifice. Under in-vivo/in-vitro conditions, animals were not pretreated with BrdUrd and colchicine was added to cells after incubation. Ascorbic-acid alone did not cause any significant change in number of SCEs. CPA or MMC alone caused about a seven fold increase in number of SCEs under both conditions. There was a dose related decrease in CPA and MMC induced SCEs with all doses of ascorbic-acid under in-vivo conditions. Under in-vivo/in-vitro conditions, there was a dose related decrease in CPA and MMC induced SCEs with doses of ascorbic-acid up to 3.34g/kg. However, in doses of 6.68g/kg, ascorbic-acid acted as a coinducer of SCEs with both CPA and MMC under in-vivo/in-vitro conditions. There were no changes in cell replication kinetics under in-vivo conditions; however, under in-vivo/in-vitro conditions, 6.68g/kg of ascorbic- acid along with CPA or MMC, caused significant cell cycle delay and toxicity. The authors conclude that CPA or MMC induced SCEs decrease with increasing concentrations of ascorbic-acid under in- vivo and in-vivo/in-vitro conditions. The paradoxical increase in SCEs at the highest dose of ascorbic-acid under in-vivo/in-vitro conditions remains unexplained. The authors postulate that ascorbic- acid has threshold levels at which it acts as an inhibitor or coinducer of SCE under culture conditions.
NIOSH-Author; Gene-mutation; Chromosome-damage; Vitamins; Carcinogens; In-vivo-studies; Laboratory-animals; Antineoplastic-agents; Hematopoietic-system
50-81-7; 50-18-0; 50-07-7
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Journal Article
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Cancer Research