Antimutagenicity of amifostine against the anticancer drug fotemustine in the Drosophila somatic mutation and recombination (SMART) test.

Amifostine (WR-2721), a phosphorylated aminothiol pro-drug, is a selective cytoprotective agent in normal tissue against the toxicities associated with chemotherapy and irradiation. Fotemustine is a cancer chemotherapeutic agent that belongs to an extremely active class of alkylating compounds. Amifostine was tested for antimutagenicity against fotemustine in the somatic mutation and recombination test (SMART) in Drosophila melanogaster. Third-instar larvae that were trans-heterozygous for the two genetic markers mwh and flr were treated at different concentrations (2, 4, and 8 microg/ml for fotemustine and, 1, 2, and 4 microg/ml for amifostine) of the test compounds; for the antimutagenicity study, 8 microg/ml fotemustine plus 1 and 2 microg/ml amifostine were tested. Fotemustine showed mutagenic and recombinagenic effects in both genotypes in the wing-spot test. Amifostine significantly reduced the mutagenic and recombinagenic effects of fotemustine.

Investigation of the genotoxic effect in bone marrow of Swiss albino mice exposed long-term to pyrimethamine.

In the present study, we investigated the genotoxic effect of pyrimethamine, which is a drug used in the therapy of toxoplasmosis and malaria, in bone marrow cells of Swiss albino mice exposed to three doses (1, 4, 8 mg/kg) of this agent for eight months orally in vivo. We used a chromosome analysis and micronucleus test for evaluation of genotoxic effect. While a statistically significant change was not determined in numerical chromosome abnormalities, structural chromosome aberrations and micronuclei were increased in a dose-dependent manner by cytogenetic and statistical evaluations.

Genotoxic, hematoxic, pathological, and biochemical effects of hexane on Swiss albino rats.

In the present study, the genotoxic, hematoxic effects, and their relation with pathological and biochemical parameters of hexane were investigated. Cytogenetic evaluation performed on the bone marrow indicated that chromosome aberrations increased at both hexane doses in relation to the negative controls. Decreased hematocrit, hemoglobin concentrations, and mean corpuscular volume were observed on the whole blood counts. Conjugated dienes (CD), glutathione (GSH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and catalase (CAT) were increased. Histological examinations showed intracytoplasmic vacuolisation, nuclei with lower chromatin, and parenchymatous degenerations in the dose groups. In the bone marrow slides, depletion of the erythroid series were observed. In conclusion, hexane seems to be a genotoxic and hematoxic agent leading to degeneration and lipid peroxidation in exposed groups.

In vivo dominant lethal effect of pyrimethamine in male mouse germ cells.

Pyrimethamine is used for treatment of malaria and toxoplasmosis. The embryotoxicity and clastogenicity of pyrimethamine is known and our aim was to investigate its dominant lethal effect in vivo. For this purpose, we used three groups of Swiss-albino male mice and a control group. We injected males with doses of 16, 32 or 64 mg/kg pyrimethamine and housed them with 10 females/male for each mating interval. Females were sacrificed and their uteri were evaluated for dominant lethality. As a result of this study we found that pyrimethamine induced dominant lethal mutations in the third, fourth and sixth weeks at the 64 mg/kg dose level, without the effect being dose-dependent. We conclude that pyrimethamine is a suspected germ cell mutagen.

The cytogenetic effects of pyrimethamine on male mouse germ cells.

Pyrimethamine is an inhibitor of dihydrofolate reductase and is used in the treatment of malaria and toxoplasmosis. We examined the cytogenetic effects of this drug. Adult male mice were given doses of 20, 40, 80, and 120 mg/kg pyrimethamine intraperitoneally. Animals were killed by cervical dislocation on the 3rd, 6th, 9th, and 12th day after treatment, and the primary spermatocytes were harvested from their testes. These cells were analyzed for gaps, breaks, acentric fragments, and exchanges, as well as for numerical aberrations such as univalency. A dose-related increase in chromosomal aberrations was found in the pyrimethamine group compared with the control group. We suspect that pyrimethamine is a possible clastogen that may affect human germ cells.