INTERCORRELATIONS AND SOURCES OF VARIABILITY IN 3 MUTAGENICITY ASSAYS- A POPULATION-BASED STUDY

The purpose of this study was to evaluate the intercorrelation between three genetic assays in 112 subjects. The group was pooled from two o riginally separate but homogeneous subgroups of 56 persons each. Proce dures included assays for hprt mutant frequencies, micronuclei in huma n lymphocytes, and mutations at the glycophorin A (gpa) loci. We found no statistically significant or biologically important intercorrelati ons among the three biomarkers. We did, however, observe significant c orrelations between log(e) hprt mutant frequency and cloning efficienc y (inverse correlation for these 2 variables), age and log(e) hprt mut ant frequency, an inverse relationship between cloning efficiency and age, and an important differential sex effect favoring a greater micro nuclei frequency in females than males. No significant correlations be tween the covariates of interest and glycophorin A variant frequencies NN or NO were observed, Using multivariable linear regression, age wa s found to account for the majority of the variability in hprt mutant frequency (greater than sex and/or smoking); for micronuclei data, onl y sex contributed a statistically significant and biologically importa nt proportion to the total variation. We conclude that despite observi ng no significant intercorrelations between the three assays performed simultaneously from the same individuals in a large population databa se, a significant correlation between age and hprt mutant frequency an d an inverse association between cloning efficiency and hprt do exist; furthermore, we verified the strong differential sex-specific effect on micronucleus frequencies.