Reaction of the carcinogen 4-hydroxyaminoquinoline 1-oxide with sulfhydryl groups of proteins

Abstract

Reaction of 4-hydroxyaminoquinoline 1-oxide (4HAQO) with sulfhydryl groups of albumin and enzymes with different types of sulfhydryl groups was studied by direct determination of unreacted sulfhydryl groups and by measurement of enzyme activities. Sulfhydryl groups of albumin, catalase, and alcohol dehydrogenase were markedly consumed in the presence of 4HAQO, and the consumption was clearly dependent on the concentration of 4HAQO. The activities of catalase, alcohol dehydrogenase, and urease were inhibited in the presence of 4HAQO, but the activity of pancreatic lipase was not affected by 4HAQO. The inhibition of these enzymes with similar molar ratios of 4HAQO to sulfhydryl groups varied as follows: catalase > alcohol dehydrogenase > urease. Inhibition of alcohol dehydrogenase and urease was almost completely reversed by the addition of glutathione, but the effect of glutathione on the inhibition of catalase was not studied. The insensitivity of lipase to 4HAQO was probably due to inaccessibility of the sulfhydryl groups to 4HAQO, for the enzyme was inhibited markedly by p-chloro-mercuribenzoate, but not by iodosobenzoate under the same experimental conditions. The different sensitivities of sulfhydryl groups in other enzymes to 4HAQO appear to be related to the differences in the locations of the sulfhydryl groups in the enzyme molecules. The reactions of sulfhydryl groups of proteins with 4HAQO may be significant in the mechanism of 4HAQO carcinogenesis.