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Quinoline: conversion to a mutagen by human and rodent liver.

Authors
Hollstein-M; Talcott-R; Wei-E
Source
J Natl Cancer Inst 1978 Feb; 60(2):405-410
NIOSHTIC No.
00076983
Abstract
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.
Keywords
NIOSH-Publication; NIOSH-Grant; Training; Preservatives; Quinolines; Industrial-chemicals; Carcinogens; Mutagens; Biochemistry; Bacteria; Enzymatic-reaction; Metabolism
Contact
Public Health University of California 108 Earl Warren Hall Berkeley, Calif 94720
CODEN
JNCIAM
CAS No.
91-22-5; 91-22-5; 578-67-6; 148-24-3; 11097-69-1; 9037-52-9; 56-49-5; 50-06-6; 58-27-5; 128-37-0; 70-18-8; 141-05-9
Publication Date
19780201
Document Type
Journal Article
Funding Amount
608432.00
Funding Type
Grant
Fiscal Year
1978
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T01-OH-00020
Issue of Publication
2
ISSN
0027-8874
Source Name
Journal of the National Cancer Institute
State
CA
Performing Organization
University of California Berkeley, Berkeley, California
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