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Hepatocyte-mediated production of sister chromatid exchange in co-cultured cells by acrylonitrile: evidence for extra cellular transport of a stable reactive intermediate.

Abstract
To study the possibility that liver metabolism of acrylonitrile (ACN) could produce a stable carcinogenic metabolite that causes the brain tumors produced by ACN, the ability of hepatocytes to generate a stable transportable mutagenic metabolite in culture was studied. ACN did not produce sister chromatid exchanges (SCEs) in Chinese hamster ovary (CHO) cells, but a significant increase was produced when CHO cells were co-cultured with freshly isolated rat hepatocytes. Induction of SCE in CHO cells co-cultured with hepatocytes suggests that the liver cells metabolize ACN and the reactive metabolite is transported from them to the CHO cells.
AuthorsS V Brat, G M Williams
JournalCancer letters (Cancer Lett) 1982 Nov-Dec Vol. 17 Issue 2 Pg. 213-6 ISSN: 0304-3835 [Print] Ireland
PMID7165873 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Nitriles
  • Acrylonitrile
Topics
  • Acrylonitrile (metabolism, pharmacology)
  • Animals
  • Biological Transport
  • Biotransformation
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Crossing Over, Genetic (drug effects)
  • Female
  • Liver (metabolism)
  • Nitriles (pharmacology)
  • Ovary
  • Rats
  • Sister Chromatid Exchange (drug effects)

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