Evaluation of flutamide genotoxicity in rats and in primary human hepatocytes.

Flutamide, an effective competitive inhibitor of the androgen receptor used orally for palliative treatment of prostatic carcinoma and regulation of prostatic hyperplasia was evaluated for its genotoxic effects in the intact rat and in primary cultures of human hepatocytes. Negative responses were obtained in all the in vivo assays as well as in the in vitro assay. In rats given a single oral dose of 500 mg/kg flutamide, fragmentation and repair of liver DNA were absent, and no increase was observed in the frequency of micronucleated hepatocytes.

Evaluation of auramine genotoxicity in primary rat and human hepatocytes and in the intact rat.

Auramine, a dye previously found to be a liver carcinogen in both mice and rats, was evaluated for its DNA-damaging and clastogenic activities in primary cultures of rats and human hepatocytes and for the induction of DNA single-strand breaks in the liver and urinary bladder mucosa of intact rats. A similar dose-dependent frequency of DNA fragmentation was revealed by the alkaline elution technique in metabolically competent primary cultures of both rat and human hepatocytes exposed for 20 h to subtoxic concentrations ranging from 10 to 32 microM. In contrast, neither rat nor human hepatocytes displayed an increased frequency of micronuclei after a 48-h exposure to the same auramine concentrations.

Testing of p-dichlorobenzene and hexachlorobenzene for their ability to induce DNA damage and micronucleus formation in primary cultures of rat and human hepatocytes.

The genotoxicity of p-dichlorobenzene (DCB) and hexachlorobenzene (HCB) was evaluated in primary cultures of rat and human hepatocytes. DNA fragmentation was measured by the alkaline elution technique and clastogenic activity by the increase in micronucleus formation. In rat hepatocytes, exposure to concentrations of DCB ranging from 0.

Testing of metoclopramide and procainamide for their ability to induce genotoxic effects in cultured mammalian cells.

Metoclopramide (MCA) and procainamide (PCA), two widely used benzamide drugs developed before the present regulatory climate but recently found to induce DNA breaks in human lymphocytes, were evaluated for their genotoxic effects in cultured rodent and human cells. In subtoxic concentrations neither MCA (from 0.10 to 0.

In vitro and in vivo testing of hydralazine genotoxicity.

Hydralazine (HDZ), a p.o. effective antihypertensive drug, was evaluated for its genotoxic effects in both rodent and human cultured cells and in the intact rat.

Comparison of micronucleus formation in mouse bone marrow and spleen.

The frequencies of micronucleated erythrocytes were compared in bone marrow and spleen of mice killed 24 and 48 h after a single i.p. dose of one directly acting carcinogen, N-nitroso-N-ethylurea (NEU, 100 mg/kg), and two indirectly acting ones, N-nitrosodimethylamine (NDMA, 50 mg/kg) and 7,12-dimethylbenz[a]anthracene (7,12-DMBA, 50 mg/kg).