Studies on the mechanisms of induction of N-nitrosodimethylamine demethylase by fasting, acetone, and ethanol

Kenneth W. Miller, Chung S. Yang

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

Previous work has shown that induction of a high-affinity NADPH-dependent nitrosodimethylamine demethylase (NDMAd) in liver microsomes occurs in rats due to fasting, ethanol consumption, and streptozotocin-induced diabetes. Several lines of observations suggest that this is due to the induction of specific cytochrome P-450 isozymes. Induction of P-450 species by ethanol has also been observed by other investigators. Since each of the above altered metabolic states has in common elevated levels of ketone bodies, the possible role of acetone, a known inducer of NDMAd, in the induction of the demethylase activity was investigated. Levels of endogenous acetone in fasted rats correlated (r = 0.72) with a three- to fourfold increase in NDMAd activity. However, a dose-response experiment showed endogenous levels of acetone to be capable of causing at most 40% of the induction in fasted rats. This suggests that other ketone bodies or factors may have contributed to the induction. The induction of NDMAd by ethanol was enhanced by alcohol dehydrogenase inhibitors pyrazole and acetaldehyde oxime, suggesting that ethanol, rather than its metabolites, was responsible for the induction.

Original languageEnglish (US)
Pages (from-to)483-491
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume229
Issue number1
DOIs
StatePublished - Feb 15 1984

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Studies on the mechanisms of induction of N-nitrosodimethylamine demethylase by fasting, acetone, and ethanol'. Together they form a unique fingerprint.

Cite this