Search

The genotoxic effects of airborne particulate samples collected from two urban areas during various traffic intensity levels were evaluated using the yeast Saccharomyces cerevisiae (D7 strain) and Salmonella typhimurium (TA98 and TA100 strains). Standard protocols were used, in compliance with recent legislation. Airborne particulate data reveal that genotoxic effects were more evident in the samples collected in the area with intense moving traffic than in the area with limited traffic. Particulate, benzene, toluene, NO2, CO, and heavy metal determinations in these two areas show that their concentrations are related to the intensity of traffic.

Two commercial preparations of atrazine and zineb were tested on a diploid D7 strain of the yeast Saccharomyces cerevisiae using cells from logarithmic growth phase (with a high level of cytochrome P-450) and from stationary growth phase. The compounds induced marked increases of both gene conversion and point mutation frequencies in the logarithmic phase cells, while in the stationary phase no genotoxic effect was observed. The results obtained employing TA98 and TA100 strains of Salmonella typhimurium (Ames test) confirmed that neither atrazine nor zineb were mutagenic. The interaction between zineb and chlorophyllin, a known antimutagen in several biological systems, has been evaluated in yeast cells from logarithmic growth phase. The results showed that chlorophyllin seems to have a protective role against the genotoxic effects of zineb. The in vivo effects on cytochrome P-450 content (Cyt. P-450) and on monooxygenase activities were examined in hepatic microsomes of induced animals (rat, pig, and rabbit) 24 hrs after acute treatment. The results obtained with atrazine showed that it caused different effects in the three animal species. Preliminary data with zineb indicated that it can act both as an inducer or as an inhibitor of the monooxygenase system, depending on the dose used.

The effects of 50 Hz, 1.2 mT magnetic fields (MFs) were tested on hepatic monooxygenase enzymes of basal and beta-naphthoflavone-phenobarbital-preinduced rats and mice. An inductive effect on cytochrome P-450 level and on some enzymatic cytochrome P-450-dependent activities was observed in basal mice after MF exposure. Enzymatic activities in preinduced mice and rats were reduced by MFs, the degree of reduction depending on the enzyme. A specific inhibitory effect was determined in some of the assayed activities and in the relative peculiar P-450 isoforms detected by Western blot analysis.

Yeast cells (D7 strain) incubated in the presence of 5-methoxypsoralen (5-MOP) increase the activity of the monooxygenase system cytochrome P-450 dependent (cytochrome P-450 level and 7-ethoxycoumarin-O-diethylase activity). Northern analysis of cytochrome P-450 specific RNA shows that 5-MOP treatments induce an increase in mRNA. The induction of cytochrome P-450 appears to occur at the transcriptional level. The capacity of 5-MOP to induce the cytochrome P-450 system in eukaryotic cells, in which it is known to be involved in the metabolism of the psoralen, may decrease the availability of the compound for photo-induced genotoxic reactions, which may explain the good tolerance in patients.

Humans are exposed daily to electromagnetic fields (EMFs) originating from a variety of devices and systems. During the 1980s many reports of potential mutagenic, teratogenic, and carcinogenic effects of EMFs were published, sometimes with contrasting results. To date, no study has established unequivocally a causal relationship between EMFs and cancer. Cell cultures can provide a simple and inexpensive tool for the study of the effects of EMFs. We have used the Chinese hamster V79 cell line to evaluate the influence of a sinusoidal EMF at 50-Hz with a constant flow of 2 G on the induction of HGPRT- mutants and on survival. Our results showed that the EMF employed did not induce any modification of mutation frequency, but the results on survival were contrasting. When only 10(2) cells were plated, a reduction in the number of colonies, reaching about 50% after 10 days of treatment, was observed; however, when 2 x 10(5) cells or more were seeded, no reduction in viability was recorded. An intercellular metabolic interaction may explain these results.

Incubation of diploid D7 strain cells of Saccharomyces cerevisiae (grown in 20% glucose) in the presence of ammonium metavanadate (AMV) led to a decrease in the cytochrome P-450-dependent monooxygenase system (cytochrome P-450 level and 7-ethoxycoumarin O-deethylase). The electrophoretic analysis of microsomal fractions of yeast cells treated with metavanadate revealed a decrease in the intensity of the bands corresponding to a M(r) in the range of 51,000-58,000 Da compared with those observed in controls, i.e., cells grown in 20% glucose. Analysis of the cytochrome P-450 transcript showed that AMV treatment reduced the mRNA level. Our results suggest that AMV inhibits the yeast cytochrome P-450 system by acting at both the pre- and post-transcriptional levels.

In Saccharomyces cerevisiae a number of chemical agents induce synthesis of cytochrome P450. A cytochrome P450 gene has been well characterized in this yeast: CYP51, which codes for a constitutive enzyme involved in the 14 alpha-demethylation of lanosterol, a key step in the biosynthesis of ergosterol. In this work, we have analysed the level of transcription of the CYP51 gene in correlation with cytochrome P450 enzymatic activity after treatment with several chemical agents known to interact with cytochrome P450. Using as a probe a DNA fragment whose identity to the CYP51 gene was established by sequence analysis and mapping on chromosome VIII, a unique RNA species was observed in all treatment samples. The increased level found for this transcript in cells treated with ethanol, 20% glucose, phenobarbital or 5-methoxypsoralen correlates with the levels of induction in cytochrome P450 enzymatic activity measured in cells grown under the same conditions, indicating that induction of cytochrome P450 by these treatments is regulated at the transcriptional level.