Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quinoline in the presence of microsomal activation exhibits mutagenic activity in Salmonella typhimurium TA100 and induces unscheduled DNA synthesis (UDS) in rat hepatocytes. Structure-activity studies were performed to determine those positions on quinoline critically associated with its genotoxicity. In assays performed to determine the ability of 2-, 4-, 6- and 8-methylquinoline to induce UDS, only 4- and 8-methylquinoline produced a positive response. This represents an improved correlation for these methylquinolines with tumorigenic activity as compared to that previously observed with mutagenic activity in S. typhimurium TA100. The complete isomeric series of fluoroquinolines were evaluated as mutagens in S. typhimurium TA100 and for their potential to induce UDS in rat hepatocytes. The only isomers that did not exhibit significant mutagenic activity were 2- and 3-fluoroquinoline. Among these isomeric fluoroquinolines 5-, 6-, 7- and 8-fluoroquinoline are capable of inducing UDS. No significant effect on UDS was observed for 2-, 3- or 4-fluoroquinoline. These data indicate that positions 1-3 in quinoline are critical sites associated with its genotoxicity.
Carcinogenesis 1991 Feb
PMID:Genotoxicity of fluoroquinolines and methylquinolines. 199 88

Quinoline, a hepatocarcinogen, mutates the bacterial tester strains in the presence of the rat liver microsomal enzymes and induces GST-P (placental glutathione S-transferase)-positive foci in a medium-term bioassay system for hepatocarcinogenesis. On the other hand, 3-fluorinated quinoline was neither mutagenic nor carcinogenic in the same assay systems, whereas, 5-fluoroquinoline was mutagenic and carcinogenic. Quinoline was recently demonstrated to be mutagenic in an in vivo mutagenicity assay system using the lacZ-transgenic mouse (MutaMouse). The present study was undertaken to know whether 3-fluoroquinoline would be devoid of in vivo mutagenicity in MutaMouse. Quinoline and 5-fluoroquinoline were also tested in the same system. Mutagenicity was evaluated in the liver, the target organ of quinoline carcinogenesis, and also in the bone marrow and testis. The results strongly indicate that fluorine-substitution at the position-3 of quinoline could be an anti-genotoxic structural modification of quinoline in a wide range of its genotoxic end-points.
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PMID:Antimutagenic structural modification of quinoline assessed by an in vivo mutagenesis assay using lacZ-transgenic mice. 963 Jun 5