Influence of strain and stage of development on three enzymes in the tryptophan to nicotinamide adenine dinucleotide pathway of mice

Abstract

In an attempt to obtain an animal model to study the carcinogenicity and toxicity of the endogenously synthesized orthoaminophenols L-3-hydroxykynurenine and 3-hydroxyanthranilate, ten inbred strains of mice were examined with respect to sex, stage of development, and strain variability for differences in hepatic levels of activity of kynurenine formamidase, hydroxykynureninase, and hydroxyanthranilate oxygenase. No significant differences for these three enzymes were found between males and females. Kynurenine formamidase and hydroxykynureninase increased in activity five-to tenfold from birth to maturity (∼30 days), whereas hydroxyanthranilate oxygenase remained at a constant high level of activity (300 to 1500 times that of hydroxykynureninase) throughout this period. Genetic regulation of kynurenine formamidase was indicated by the finding that when a strain with high activity was crossed to a strain with low activity, the F1 hybrid had an intermediate level of activity. Some differences in activity among strains were found for hydroxykynureninase, but it remains to be seen whether these differences may also be genetically determined. No significant differences in the level of activity were found among strains for hydroxyanthranilate oxygenase.