Related Experiment Videos
Quinoline: conversion to a mutagen by human and rodent liver
Journal of the National Cancer Institute
|February 1, 1978
Summary
Quinoline and its derivatives can be mutagenic, particularly after metabolic activation by liver enzymes. This mutagenicity is linked to specific metabolites and can be influenced by protective agents and enzyme induction.
Area of Science:
- Toxicology
- Biochemistry
- Carcinogenesis
Background:
- Quinoline is a known hepatocarcinogen in rats.
- Understanding the metabolic activation and mutagenicity of quinoline is crucial for assessing its health risks.
Purpose of the Study:
- To investigate the mutagenic potential of quinoline and its derivatives using the Ames Salmonella typhimurium assay.
- To identify the metabolic pathways and reactive intermediates involved in quinoline-induced mutagenicity.
- To explore the role of specific enzyme systems and protective agents in modulating quinoline's mutagenic activity.
Main Methods:
- Ames Salmonella typhimurium assay with TA 100 strain.
- Use of Aroclor 1254-induced rat liver homogenate and enzyme preparations from pretreated rats and mice.
- Investigation of protective effects using various compounds (menadione, BHT, alpha-naphthoflavone, vitamin A acetate, glutathione).
- Assessment of glutathione depletion effects using diethyl maleate.
- Analysis of water-soluble quinoline metabolites.
- Testing of human liver and lung microsomal enzymes.
Main Results:
- Quinoline, 5-hydroxyquinoline, and 8-hydroxyquinoline showed mutagenicity in the presence of rat liver homogenate.
- Enzyme preparations from rats and mice treated with aryl hydrocarbon hydroxylase inducers (MCA, beta-naphthoflavone) metabolized quinoline to a mutagen.
- Phenobarbital and pregnenolone-16alpha-carbonitrile pretreatment did not yield active preparations.
- Mutagenicity was inhibited by menadione, BHT, alpha-naphthoflavone, vitamin A acetate, and glutathione.
- Glutathione depletion enhanced mutagenic potential.
- Mutagenic activity correlated with water-soluble metabolites, suggesting quinoline-2,3-epoxide as a reactive intermediate.
- Human liver microsomal enzymes, but not lung enzymes, converted quinoline to a mutagen.
Conclusions:
- Quinoline and some derivatives exhibit mutagenic activity mediated by specific metabolic activation pathways.
- The formation of quinoline-2,3-epoxide is implicated as the reactive mutagenic intermediate.
- Enzyme induction and protective agents significantly influence quinoline's mutagenicity.
- Human liver enzymes can activate quinoline to a mutagen, highlighting potential human health risks.