Bone marrow cell chromosomal aberrations and styrene biotransformation in mice given styrene on a repeated oral schedule.

Styrene's capacity to induce chromosomal aberrations was studied in bone marrow cells of CD1 male mice. No mutagenic effect could be detected after either a 4-day treatment course with daily oral doses of 500 mg/kg or a 70-day course with daily oral doses of 200 mg/kg. Urinary elimination of styrene metabolites related to styrene-7,8-oxide formation (i.e. phenylethylene glycol, mandelic acid, benzoic acid, phenylglyoxylic acid and total mercapturic acids) was quantitatively evaluated in the group of mice given the 200 mg/kg dose. In parallel, kinetic studies were made on styrene and styrene-7,8-oxide blood concentrations in the same group of animals. These determinations were carried out on days 1 and 70 of treatment by spectrophotometric, gas chromatographic and mass fragmentographic procedures. Not even nanograms of styrene-7,8-oxide were found in the blood of styrene-treated mice. This suggests that the metabolite does not migrate from the cellular compartment where it is formed being immediately metabolized or irreversibly bound to cellular structures. This observation could well explain the lack of mutagenic effects observed.

Human lymphocytes assay: cyclophosphamide metabolic activation by S9 system with low cytotoxicity.

The general suitability of exposing human lymphocytes directly to prolonged contact with an Ames-type microsomal (S9) activation system has been examined, for testing the effect of the indirect chemical mutagen, cyclophosphamide (CPA), on induction of chromosomal aberrations. Direct exposure of lymphocytes to only S9 mix produced a decrease in the mitotic index within 30-60 min, whereafter it stabilized at acceptable values. Further toxic effects following treatment with different doses of CPA and S9 mix, for the longest times of exposure were due to production of clastogenic metabolites. On the basis of these results, the low cytotoxicity of S9 mix in our conditions allows extension of the application of the test to the study of metabolites which require prolonged contact with the target cells.

Chromosomal monitoring of chromium-exposed workers.

A cytogenetic analysis was carried out on peripheral blood lymphocytes of workers exposed to chromite in a ferrochromium plant, to evaluate the possible existence of genetic damage. A quantitatively limited increase in aberrant cell frequencies was detected in subjects working in the furnace sector. The data were analyzed by several statistical approaches.

Genotoxicity, metabolism and blood kinetics of epichlorohydrin in mice.

Epichlorohydrin (ECH), a direct mutagen in vitro, did not induce chromosomal aberrations in bone-marrow cells of CD1 mice given single oral doses of 50 and 200 mg/kg in water. The ECH diol derivative (3-chloro-1,2-propanediol) was tested in vitro by a forward-mutation assay on the yeast Schizosaccharomyces pombe and showed a weak but significant mutagenic effect. The failure of ECH to induce mutagenic effects appears to be due to the rapid metabolic clearance of the compound in vivo. ECH blood kinetics at both doses, and at the same time the concentration of the diol, were determined. ECH rapidly disappeared from mouse blood, being no longer detectable 20 min after treatment. In contrast, 3-chloro-1,2-propanediol was measurable up to 5 h after dosage. No difference was observed in the kinetic and metabolic behavior of ECH after single and repeated doses (50 and 200 mg/kg/day for 7 days). When 3-chloro-1,2-propanediol was tested, neither glutathione depletion nor epoxide hydrolase inhibition (evaluated with both styrene-7,8-oxide and ECH as substrates) could be detected in mouse liver. Finally, no difference in ECH blood kinetics or metabolism were observed in experiments in which the compound was administered (200 mg/kg) intraperitoneally in water or orally as a solution in dimethyl sulfoxide.

The karyotypes of the Corsican and Sardinian mountain salamanders, Euproctus montanus and E. platycephalus (Urodela: Salamandridae).

The chromosomes of Euproctus montanus and E. platycephalus were studied by means of the C-banding method and the AS-SAT technique which are useful for identifying the single pairs of the complement and for recognizing nucleolar organizer regions. According to the morpho-structural characteristics shown by the specific karyotypes, it has been possible to draw some cytotaxonomic deductions concerning the karyological evolution within the insular group.