Activation of some aromatic amines to mutagenic products by human red blood cell cytosol.

The ability of human red blood cell cytosol to activate aromatic amines was evaluated with the Ames test using Salmonella typhimurium TA98 in the liquid preincubation condition. While negative results were obtained with 4-acetylaminofluorene (4AAF) and 1-naphtylamine (1NA), a slight response was observed for 4-aminobiphenyl (4ABP) and 2-naphthylamine (2NA). Human red blood cell cytosol was able to activate 2-aminofluorene (2AF), 2-acetylaminofluorene (2AAF) and 2-aminoanthracene (2AA) to mutagenic intermediates. Extracts of human red blood cell cytosol incubated with 2AF were analyzed by gas chromatography: N-hydroxy-2-aminofluorene was identified as a metabolite

Mutagenicity of some heterocyclic amines in Salmonella typhimurium with metabolic activation by human red blood cell cytosol.

Purified human red blood cell cytosol was used to activate the heterocyclic amines 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) into mutagenic intermediate(s) in the Salmonella test. The liquid preincubation method in the presence of strain TA98 was utilized. In order to understand the mechanism involved in this metabolic activation, some modulators were incorporated in the medium. The results suggest that an oxygenated hemoprotein, probably oxyhemoglobin, is involved in the activation into genotoxic intermediate(s)

Effect of age on the ability of rat liver tissues to transform chemical promutagens to mutagens.

Age-related changes in drug metabolism of the liver from male Lou rats were determined by measuring changes in the production of mutagens. Activation of aflatoxin B1 (AFB1), 2-aminoanthracene (2AA) and benzo[a]pyrene (B[a]P) to mutagenic derivatives was assayed using the Ames salmonella test system. The promutagens were incubated with tissue fractions isolated from rats ranging in age from 3 weeks to 18 months. Hepatic activation of AFB1 and 2AA changes with age and is maximal from 4 to 10 months. In contrast, no significant modification with age was observed for the activation of B[a]P. It is concluded that the composition of different cytochrome P-450 fractions is modified with age thereby altering the specific ability to convert different promutagens to mutagens

No evidence for radiation-induced clastogenic factors after in vitro or in vivo exposure of human blood.

Experiments were performed with human plasma irradiated in vitro or in vivo in order to evaluate the extent to which clastogenic factors might disturb the adaptive response to DNA-damaging factors currently studied in our laboratory. The studies were carried out with plasma isolated from whole blood given 4 Gy of X-rays in vitro and with plasma from people receiving local radiotherapy at a total dose of about 60 Gy gamma rays. Addition of irradiated plasma to culture medium did not result in a statistically significant increase in structural aberrations in chromosomes of non-irradiated normal blood

Evaluation of the ability of paracetamol to produce chromosome aberrations in man.

The ability of paracetamol to induce structural chromosome aberrations in human peripheral blood lymphocytes in vivo was evaluated in volunteers who had been administered a single oral dose of 3 g paracetamol, in patients who had received 2 g of propacetamol by intravenous infusion every 6 h for at least 7 days, and in self-poisoned patients who, for suicidal reasons, had ingested more than 15 g paracetamol. In addition to the in vivo observations, the effectiveness of paracetamol to interfere with fusorial microtubule polymerisation was assayed in vitro in order to detect a possible effect of paracetamol on the distribution of chromosomes during cell division. The negative results obtained in all those assays strongly suggest that paracetamol has no mutagenic properties in human. There was, indeed, no significant difference in the percentage of abnormal cells before and after application of paracetamol in volunteers (0.2% before ingestion of 3 g paracetamol, 0.12% after 24 h, 0.04% after 72 h and 0.04% after 168 h) and in patients (0.5% of abnormal cells before treatment versus 0.44% after intravenous infusion of a total of 28 g paracetamol). Moreover, the yield of abnormal cells was not modified in self-poisoned persons (0.24%), in spite of an important decrease in the mitotic index of the PHA stimulated lymphocytes. In the in vitro assay, no inhibition of microtubule polymerisation was detected with concentrations of 2.5, 5 and 10 mM paracetamol