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The clastogenic and mutagenic effects of ascorbigen and 1'-methylascorbigen

S R Musk1, M N Preobrazhenskaya, G A Belitsky

  • 1AFRC Institute of Food Research, Norwich Laboratory, Colney, UK.

Mutation Research
|January 1, 1994
PubMed
Summary

Natural ascorbigen showed no cytotoxic or mutagenic effects in cell and bacterial assays. However, synthetic 1'-methylascorbigen demonstrated significant cytotoxicity, induced sister-chromatid exchanges, and caused mutations in the Ames test.

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Area of Science:

  • Toxicology
  • Genetics
  • Biochemistry

Background:

  • Ascorbigen is a naturally occurring compound found in the human diet.
  • Synthetic analogues of natural compounds are often developed for research and therapeutic purposes.
  • Understanding the genotoxic potential of dietary compounds and their analogues is crucial for public health.

Purpose of the Study:

  • To evaluate the cytotoxic, clastogenic, and mutagenic activities of ascorbigen and its synthetic analogue, 1 -methylascorbigen.
  • To compare the genotoxic profiles of the natural compound and its synthetic derivative.
  • To assess the safety and potential risks associated with these compounds.

Main Methods:

  • Cytotoxicity and clastogenicity assays were performed using a SV40-transformed Indian Muntjac cell line (SVM).

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  • Mutagenic activity was assessed using the Ames test with Salmonella typhimurium strains TA98 and TA100.
  • Standard toxicological and genotoxicological testing protocols were followed.

    • Main Results:

    • Ascorbigen exhibited no cytotoxic effects below 0.21 mg/ml and did not induce chromosome aberrations, sister-chromatid exchanges (SCEs), or mutations.
    • 1 -methylascorbigen was significantly more cytotoxic (Dq = 0.03 mg/ml) than ascorbigen.
    • 1 -methylascorbigen induced SCEs in SVM cells at highly cytotoxic doses and demonstrated mutagenic activity in the Ames test.

    Conclusions:

    • Natural ascorbigen appears to be non-genotoxic and safe at tested concentrations.
    • Synthetic 1 -methylascorbigen exhibits significant genotoxic potential, including cytotoxicity, SCE induction, and mutagenicity.
    • The structural modification in 1 -methylascorbigen drastically alters its toxicological profile compared to the natural compound.