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

Details

• Personal Author:
  Krishna G ; Nath J ; Ong T
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Antineoplastic Agents Carcinogens Chromosomes Hematopoietic System Laboratories Occupational Health Safety
• Keywords:
  Antineoplastic-agents Chromosome-damage Gene-mutation Hematopoietic-system In-vivo-studies Laboratory-animals NIOSH-Author Vitamins
• ISSN:
  0008-5472
• Document Type:
  Text
• Genre:
  Journal Article
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  46
• Issue:
  6
• NIOSHTIC Number:
  nn:00167172
• Citation:
  Cancer Res 1986 Jun; 46(6):2670-2674
• CAS Registry Number:
  Cyclophosphamide (CAS RN 50-18-0) ; L-Ascorbic acid (CAS RN 50-81-7) ; Mitomycin C (CAS RN 50-07-7)
• Federal Fiscal Year:
  1986
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0fe22ab4bcf9a1f2d6386513baa505bd01494cecf94648a0b935cb445f1e73fad871b234f5e60cb88e49a3efc19f91c3334695392d7c862920ec60e4190bd16d
• Download URL:
  https://stacks.cdc.gov/view/cdc/185127/cdc_185127_DS1.pdf
• File Type:
  [PDF - 372.77 KB ]