P XV.4 4-Chloro-o-phenylenediamine a 26-week oral (in feed) mutagenicity study in Big Blue™” mice (original) (raw)

A lambda ell positive selection was introduced (Jilkubczak et al., 1996) to assess gene mutations using BigBlueGll transgen ic mice. In contrast to the color select ion method, the positive selection method increased the performance of the assay. We compared mutant frequen cy (MF) and mutation spectra of dimethylnitrosamine (DMN) between ell and lael genes. DMNinduced MF in ell (2S.8 X 10-5) was higher !han in lael (10 .7 x 10-5) as well as spontaneous MF (9.S x 10-5 in ell and 1.7 x 10-5 in lacl). The mutat ion spectra wert also different between ell and lacl genes. One base insertion at GGGGGG site was predominant in spontaneous ell mutants. One base delet ion as well as insertion at this site was also observed in DMN-induced mutants. In addition, DMN-induced mutants showed G:C to A:T trans itions in ell gene probably through d-methyl guan ine. On the other hand, deletions more than I-base were predominant among DMN-induced loci mutants as well as G:C to A:T transitions. A similar analysis is ongoing on MelQx-induced mutants.