Antimutagenic effect of phenethyl isothiocyanate.

Using the Ames bacterial mutagenicity test, the comet assay, and an in vivo micronucleus test, we investigated the effect of the chemoprotective substance phenethyl isothiocyanate (PEITC) on the mutagenic activity of indirect-acting mutagens and carcinogens aflatoxin B1 (AFB1) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), and direct-acting mutagen and carcinogen N-nitroso-N-methylurea (MNU). In the Ames test, the antimutagenic activity of PEITC was studied in the concentration range 0.3-300 microg/plate. PEITC at concentrations of 0.3, 3 and 30 microg/plate reduced dose-dependently mutagenicity of AFB1 and IQ in both S. typhimurium TA98 and TA100 strains. In the case of the direct mutagen MNU, the antimutagenic effect of PEITC was detected only at concentration of 30 microg/plate in the strain TA100. The PEITC concentration 300 microg/plate was toxic in the Ames test. The 24 h pre-treatment of HepG2 cells with PEITC at concentration 0.15 microg/ml resulted in a significant decrease of DNA breaks induced by MNU at concentrations 0.25 and 0.5 mM. Although a trend towards reduced strand break level were determined also at PEITC concentrations 0.035 and 0.07 microg/ml it did not reach the statistical significance. No effect, however, of PEITC on IQ-induced DNA breaks was observed. Chemopreventive effect of PEITC was revealed also in vivo. Pretreatment of mice with PEITC concentrations of 25 and 12.5 mg/kg b.w. administered to mice in three daily doses resulted in reduction of micronucleus formation in mice exposed to all three mutagens under study, with statistically significant effect at concentration of 25 mg/kg. Results of this study indicate that the strong PEITC antimutagenic properties may have an important role in the prevention of carcinogenesis and other chronic degenerative diseases that share some common pathogenetic mechanisms.

Micronuclei, DNA single-strand breaks and DNA-repair activity in mice exposed to 1,3-butadiene by inhalation.

We investigated single-strand breaks and endonuclease III-sensitive sites in DNA along with gamma-irradiation-specific DNA-repair activity in hepatocytes and frequencies of micronuclei in polychromatic bone-marrow erythrocytes of male NMRI mice (2 months old, weight 30-35 g) during sub-acute inhalation exposure to 1,3-butadiene (28 days, 500 mg/m3) and up to 28 days after the exposure. Concentrations of 1,3-butadiene in blood, an indicator of internal exposure, moderately increased during the exposure period. The most interesting finding was that gamma-irradiation-specific DNA-repair activity gradually increased during exposure, being significantly higher compared with control levels on days 7 and 28 of exposure (P = 0.005 and 0.035, respectively), reaching a maximum on day 1 after the termination of exposure (P = 0.003) and then returning to control levels. A significant correlation between gamma-irradiation-specific DNA-repair activity and the concentration of 1,3-butadiene in blood (R = 0.866, P = 0.050) supports a possible induction of DNA-repair activity by the exposure to 1,3-butadiene and formation of its metabolites. The initial increase in micronucleus frequency (micronuclei per 1000 cells) in the exposed mice continuously decreased from 20.4 +/- 5.1 (day 3) to 15.1 +/- 3.2 (day 28) within the exposure period, and subsequently from 12.4 +/- 5.1 to 4.6 +/- 1.6 in the period following termination of the 1,3-butadiene exposure, while micronucleus frequencies in control animals were significantly lower (from 1.7 +/- 1.5 to 4.2 +/- 0.8).

A re-assessment of styrene-induced clastogenicity in mice in a subacute inhalation study.

To date, a number of in vivo cytogenetic assays have studied the clastogenicity (chromosome aberrations, micronuclei formation) in bone marrow of rodents exposed to styrene by various routes. The majority of all these cytogenetic experiments yielded negative findings (Scott and Preston, Mutat Res 318:175-203, 1994). Recently published data from a micronucleus test in mice exposed via inhalation for up to 21 days showed some positive response, but was not fully conclusive (Vodicka et al., Chem Biol Interact 137:213-227, 2001). Since this exposure regimen has considerable relevance for workplace exposure, the present study was performed to further elucidate these findings. NMRI mice were exposed by whole body inhalation to styrene concentrations of 750 mg/m3 and 1,500 mg/m3 for 1, 3, 7, 14 and 21 consecutive days (6 h/day). Animals were killed directly after exposure and bone marrow was sampled for analysis of micronucleus induction. Under the experimental conditions used in the present investigation, there was no evidence of clastogenicity at any concentration or exposure interval.