Environmental genotoxicity evaluation using cytogenetic end points in wild rodents.

We analyzed cytogenetic end points in three populations of two species of wild rodents--Akodon montensis and Oryzomys nigripes--living in an industrial, an agricultural, and a preservation area at the Itajaí Valley, state of Santa Catarina, Brazil. Our purpose was to evaluate the performance of the following end points in the establishment of a genotoxic profile of each area: the polychromatic/normochromatic cell ratio; the mitotic index; the frequency of micronucleated cells both in the bone marrow and peripheral blood; and the frequency of cells with chromosome aberrations in the bone marrow. Preparations were obtained using conventional cytogenetic techniques. The results showed a) the role of the end points used as biomarkers in the early detection of genotoxic agents and in the identification of species and populations at higher risk; b) the difference in sensitivity of the species selected as bioindicators in relation to the cytogenetic end points analyzed; c) the need to use at least two sympatric species to detect the presence of genotoxins in each locality; and d) the need to use several end points when trying to establish a genotoxic profile of an area.

Radiosensitivity of blood lymphocytes from basocellular carcinoma patients, as detected by the micronucleus assay.

Cytogenetic techniques, the micronucleus (MN) assay, in particular, have been widely used in population monitoring, biological dosimetry and early detection of groups susceptible to cancer. Individuals respond differently to several environmental agents. The efficiency of the cellular repair mechanisms would be responsible, at least to some extent, for individual differences in sensitivity to neoplasia. In order to determine the sensitivity of cancer patients to ionizing radiation, blood cultures from untreated individuals with basocellular carcinoma, young healthy subjects and older healthy subjects, were irradiated in vitro with 60Co at doses ranging from 0 to 500 cGy and submitted to the cyto-B micronucleus assay; the frequency of cells and distribution of MN and dose-response relationships were analyzed. Results showed that cancer patients had a lower frequency of cells with spontaneous MN than older healthy subjects. The frequency of micronucleated cells was not different in patients and healthy subjects, but not the distribution of MN per radiation dose: for the carcinoma group, while the proportion of cells with one MN decreases drastically, the proportion of the cells with two or more MN increases with the same intensity. Our results show that the proportion of damaged cells is similar in patients with basocellular carcinoma and healthy subjects, but the magnitude of radiation-induced lesion is greater in the cancer patients.

Evaluation of the genotoxic potential of flumethrin in mouse bone marrow by chromosomal analysis and micronucleus test.

The genotoxic potential of the pyrethroid flumethrin was evaluated by using the combined protocol of metaphase analysis and micronucleus test in vivo in mouse bone marrow. The dermal route was tested in a single treatment and the intraperitoneal (i.p.) route in a single and a multiple treatment. Flumethrin showed a cytotoxic effect on both myelopoiesis and erythropoiesis, as evidenced by a reduction in the mitotic index and in polychromatic erythrocyte values. An increase in the frequency of gaps after the dermal exposure and of breaks only at the highest dose tested in the i.p. treatment indicates a weak clastogenic potential of the compound. A significant increase in the frequency of micronucleated polychromatic erythrocytes was observed after single and multiple i.p. treatments. In the latter, the induction of micronuclei was highly significant but not accompanied by an increase in breaks. This may indicate that the clastogenic effect might not account by itself for the induction of micronuclei, which could also have arisen from an aneugenic potential of flumethrin.

Cytogenetic effects of inhaled ethylene oxide in somatic and germ cells of mice.

The induction of cytogenetic effects by inhalation of ethylene oxide was tested in bone marrow cells and primary spermatocytes at diakinesis-metaphase I cells from mouse after a single treatment (6 h/1 day) at 0, 200, 400 and 600 ppm, and multiple treatment (6 h/5 days/2 weeks) at 0, 200 and 400 ppm. Ethylene oxide induced chromosomal aberrations in both somatic as well as in germ cells of mice. In the single treatment the response observed for germ cells was not equivalent to that observed for somatic cells. In the latter there was a greater sensibility for bone marrow cells. With multiple treatment the effects on the chromosomes were equivalent in somatic and in germ cells.

The effects of age, sex and diet on the clastogenic action of cyclophosphamide in mouse bone marrow.

7-week-old and 12-week-old mice of both sexes received either a control or protein-deficient diet for 3 weeks. Afterwards, they were given a single dose of cyclophosphamide (0.5 mg/10 g b.wt.) before being sacrificed. The relationship between age and the clastogenic action of cyclophosphamide can be observed in the bone marrow cells of male mice but not in those of female mice. 12-week-old males on a 75% protein-deficient diet have a lower frequency of cells with cyclophosphamide-induced chromosome aberrations than has the control group. On the contrary, 7-week-old males and females, and 12-week-old females, show that protein-deficient diets act synergistically with the clastogenic action of cyclophosphamide. These results are discussed taking the metabolism of the drug into account. Animal age also plays a role in the formation of chromosome rearrangements; this type of aberration is significantly more frequent in younger animals of both sexes than in older ones exposed to the drug.

Cytogenetic study of workers exposed to methyl-parathion.

When compared with non-exposed controls, a group of pesticide plant workers chronically exposed to methyl-parathion did not show an increased frequency of chromosome aberrations in lymphocyte cultures. Although methyl-parathion increased chromosome aberrations in cases of intoxication, a chronic exposure to small doses in the work place did not seem to produce the same effect.

Acrylonitrile: in vivo cytogenetic studies in mice and rats.

Acrylonitrile (VCN), a suspect human carcinogen, does not produce significant increases in cytogenetic aberrations in the mouse-bone marrow when given orally for 4, 15 or 30 days at doses equal to 7, 14 and 21 mg/kg/day resp. or by i.p. for the same time periods at doses of 10, 15 and 20 mg/kg/day. Rats treated orally with 16 daily doses of VCN (40 mg/kg/day) or potassium cyanide (KCN) (5 mg/kg/day) showed no increase of aberrant metaphases in the bone marrow over controls.