Effect of pyridoxal deficiency on pancreatic DNA damage and nodule induction by azaserine

Joanne Zurio, B. D. Roebuck, Joseph V. Rutkowski, Thomas J. Curphey, Daniel S. Longnecker

Research output: Contribution to journalArticle

Abstract

The effects of pyridoxal deficiency on the genotoxlclty and nodule inducing ability of azaserine in rat pancreas were examined. Azaserine at a dose of 10 mg/kg body weight which causes substantial DNA damage in normal rat pancreas, failed to induce DNA damage detectable by alkaline elution in the pancreas of pyridoxai-deficient rats. Studies of the distribution of [14C]azaserine in rat tissues revealed that uptake of azaserine in pancreas of pyridoxal deficient rats was not significantly different from that of normal rats. The ability of a structurally unrelated amino acid carcinogen Nδ-(N-methyl-N-nitrosocarbamoyl)-L-ornithine to damage rat pancreatic DNA was not affected by pyridoxal deficiency. In another study, the pyridoxal antagonist 4'-deoxypyridoxine was administered i.p. to rats prior to and during azaserine treatment. Four months later, quantitative stereological analysis of atypical acinar cell nodules revealed that there was a significant reduction in the number but not size of nodules in the pancreases of 4'-deoxypyridoxine-treated rats. These results confirm the relationship of the induction of DNA damage by azaserine to its ability to induce pancreatic tumors, and support previous studies of azaserine metabolism, strongly suggesting that the in vivo activation of this carcinogen is pyridoxal dependent.

Original languageEnglish (US)
Pages (from-to)555-558
Number of pages4
JournalCarcinogenesis
Volume5
Issue number5
DOIs
Publication statusPublished - May 1984
Externally publishedYes

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ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience
  • Cancer Research

Cite this

Zurio, J., Roebuck, B. D., Rutkowski, J. V., Curphey, T. J., & Longnecker, D. S. (1984). Effect of pyridoxal deficiency on pancreatic DNA damage and nodule induction by azaserine. Carcinogenesis, 5(5), 555-558. https://doi.org/10.1093/carcin/5.5.555