Dominant-lethal mutations and micronucleus induction in male BALB/c, BDF1 and H mice by tobacco smoke

Abstract

The mutagenicity of whole tobacco smoke (TS) was examined in male BALB/c, BDF1 and H mice using the dominant lethal and micronucleus tests in bone marrow polychromatic erythrocytes. Male mice (about 80 days old) from the three strains were treated with TS on 5 days/week for 8 weeks. The animals were divided into three groups for every strain: control and two experimental groups. Two doses - low (1h treatment/day) and high (2 h treatment/day) - were used. In the first case 8 exposures of 7.5 min each with 1-min intervals were given and to realize the high dose this was repeated 4 h later. It was found that TS induces significant dominant-lethal mutations in both experimental groups of BALB/c, BDF1 and H mice ( p < 0.001), but some strain differences existed. The data obtained suggest that in BALB/c and BDF1 mice TS induces dominant-lethal mutations mainly in spermatocytes, spermatogonia and gonial stem cells, while in H mice only spermatids and spermatocytes are affected. The bone marrow from each strain and each dose group was investigated for the presence of micronucleated polychromatic erythrocytes (PCE) at 5, 19, 38, 54, and 63 days after beginning of the treatment with TS, using the same exposure regimen. Exposure of male mice to TS caused an up to 2–3-fold increase in the number of PCE in the bone marrow of BALB/c and BDF1 mice in both dose groups. In H mice this effect is observed only on days 19 and 38 of sampling. No cumulative or dose-dependent effects were detected. Increased formation of micronuclei within PCE of femoral bone marrow after passive smoking was regarded as being due to the effect of TS.