Induction of sister chromatid exchanges in human diploid fibroblasts by mutagens with and without rat liver microsomal activation.

Abstract

The frequency of sister chromatid exchange (SCE) in WI-38 cells was estimated by the 5-bromodeoxyuridine (BrdUrd)-dye technique after one hour's exposure to cyclophosphamide (CY), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 4-nitroquinoline-1-oxide (4NQO), and maleic hydrazide (MH) with and without the addition of rat liver microsomal suspension (S-9) fraction with cofactors (S-9 mix). CY at concentrations from 1 x 10(-5) M to 1 x 10(-3) M with S-9 mix increased the number of SCEs per cell in a dose-dependent manner. Without S-9 mix, CY at concentrations below 1 x 10(-3) M failed to produce more SCEs than the controls. MNNG at 1 x 10(-8) M and 4NQO at 1 x 10(-7) M without S-9 produced significant increases in SCEs per cell. Addition of S-9 during treatment slightly decreased the effects of MNNG and 4NQO in the formation of SCEs. MH was tested at pH 6.4 and pH 7.6. At pH 7.6, MH at 1 x 10(-3)M without S-9 mix inhibited cell multiplication, but did not cause a significant increase of SCEs per cell. There were no interactions between MH (2 x 10(-4) M) and S-9 mix nor between MH and the pH levels tested. These results indicate that in the presence of metabolic activation, SCE formation in human diploid fibroblasts in vitro may be used as a potential assay for mutagenicity.