Quinoline: conversion to a mutagen by human and rodent liver.
Hollstein-M; Talcott-R; Wei-E
J Natl Cancer Inst 1978 Feb; 60(2):405-410
Quinoline (91225), a hepatocarcinogen in rats, and 23 quinoline derivatives were tested for mutagenic activity with the ames salmonella typhimurium assay. Quinoline (91225), 5-hydroxyquinoline (578676), and 8-hydroxyquinoline (148243) were mutagenic in strain TA-100 when Aroclor-1254 (11097691) induced rat (male outbred Sprague-Dawley) liver homogenate was present in the incubation mixture. Enzyme preparations from rats pretreated with p-448 dependent aryl-hydrocarbon hydroxylase (9037529) inducers (3- methylcholanthrene (MCA) (56495) and beta-naphthoflavone) and MCA treated responsive C57BL mice also metabolized quinoline to a mutagen, but phenobarbital (50066) and pregnenolone-16alpha- carbonitrile pretreatment did not yield active preparations. The mutagenicity of quinoline was blocked by the in-vitro addition of menadione (58275), butylated-hydroxytoluene (128370), alpha- naphthoflavone, vitamin A acetate, and glutathione (70188) to the test system. Depletion of glutathione by diethyl-maleate (141059) pretreatment in-vivo enhanced the mutagenic potential of the liver enzyme preparation. Mutagenic activity was correlated to the formation of water soluble quinoline metabolites, and it is suggested that the reactive quinoline intermediate is quinoline-2,3- epoxide. Microsomal enzymes isolated from human liver tissue, but not lung tissue, also converted quinoline to a mutagen.
NIOSH-Publication; NIOSH-Grant; Training; Preservatives; Quinolines; Industrial-chemicals; Carcinogens; Mutagens; Biochemistry; Bacteria; Enzymatic-reaction; Metabolism
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