Cell specificity in metabolic activation of aflatoxin B1 and benzo(a)pyrene to mutagens for mammalian cells [22]

Robert Langenbach, Heather J. Freed, Dina Raveh, Eliezer Huberman

Research output: Contribution to journalLetterpeer-review

81 Scopus citations

Abstract

ENVIRONMENTAL chemical carcinogens are usually non-reactive and have to be enzymatically activated before they can manifest their biological effects 1-6. Many cell types, including those used for mutagenesis studies, are not capable of activating such procarcinogens; mutagenesis in these cells has been studied by the addition of an enzymatically active liver subcellular fraction7-9. However, these liver subcellular fractions readily activate a wide spectrum of compounds into potent mutagens including those which are not carcinogenic to the liver. In addition subcellular preparations differ from intact cells in the profile of the metabolites10,11 and DNA adducts12,13 formed after metabolism of various potent carcinogens such as aflatoxin B1 (AF), benzo(a)pyrene (BP), and 7,12-dimethylbenz(a)anthracene. These results suggest that the use of sub-cellular fractions does not truly simulate the in vivo situation and that it may be advantageous to use intact cells for metabolic activation of chemical carcinogens. Therefore, studies of carcinogen metabolism and mutagenic activity in cultured cells derived from different tissues should more truly reflect the in vivo situation and should also provide insight into the problem of tissue specificity in chemical carcinogenesis. Metabolic activation by intact cells of different carcinogens into intermediates which are mutagenic to mammalian cells has been reported4,14-19. This report compares the abilities of two different cell types, fibroblasts and liver cells derived from rats, to metabolise two carcinogens (BP, a potent skin and lung carcinogen which can also produce fibrosarcomas20, and AF, a potent liver carcinogen 21) to water-soluble products, to intermediates which bind to cellular DNA, and to intermediates which are mutagenic to Chinese hamster V79 cells. Ouabain resistance was used as the genetic marker in V79 cells 14,22.

Original languageEnglish
Pages (from-to)277-280
Number of pages4
JournalNature
Volume276
Issue number5685
DOIs
StatePublished - 1 Dec 1978
Externally publishedYes

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