sodium-nitrite and Lymphoma

To test the tumorigenic potential of aminopyrine, an antipyretic analgesic, it was administered in drinking water at levels of 0 (control), 0.04 and 0.08% to 50 male and 50 female B6C3F1 mice for 100 weeks, and the mice were subsequently maintained without aminopyrine for a further 4 weeks. The most frequent types of tumor, in both treated and control groups, were hepatocellular tumor in male mice and malignant lymphoma/lymphoid leukemia in female mice. No statistically significant differences were observed in the incidences of these tumors between treated and control groups. The incidences of several other tumors in male and female mice also showed no statistically significant differences between treated and control groups. Therefore, no tumorigenic effect of orally administered aminopyrine in B6C3F1 mice was apparent in the present study.

Topics: Administration, Oral; Aminopyrine; Animals; Female; Liver; Liver Neoplasms, Experimental; Lymphoma; Male; Mice; Mice, Inbred Strains; Neoplasms, Experimental; Sodium Nitrite

The genotoxicity of coal dust extract nitrosated by NaNO2 was investigated because of an elevated incidence of gastric cancer in coal miners. Human peripheral lymphocytes were used to determine the frequency of sister chromatic exchanges (SCE) and chromosome aberrations. Chinese Hamster Ovary (CHO) cells were also used to measure SCEs. The mouse lymphoma forward mutation assay comprised the final in vitro system, while the micronucleus test on mouse bone marrow cells was used as an in vivo assay. The SCE frequency in human lymphocytes increased from 9.2 per cell in untreated cultures to 31.6 per cell in cultures treated with 10.0 microliter/ml of nitrosated coal dust extract (NCDE) (P less than .0001). Chromosome aberrations were tested during two phases of the cell cycle; the results indicate that NCDE causes an increase in aberrations in each cell phase tested. The SCE frequency in the CHO system increased from 9.0 per cell in untreated cultures to 18.0 per cell in cultures treated with 3.3 microliter NCDE per ml of medium (P less than .001). In the mouse lymphoma system, the background mutation frequency was tripled at 2.0 microliter NCDE per ml of medium. NCDE was not found to be active in the murine micronucleus assay. No consistent increase in genetic activity was observed with nonnitrosated coal dust extract alone or with NaNO2 alone. Metabolic activation greatly reduced or eliminated genetic activity. These results indicate that nitrosated coal dust extract is genetically active in in vitro mammalian systems without metabolic activation. These findings suggest that the nitrosation of ingested coal dust may be responsible for the elevated incidence of gastric cancer in coal miners.

Topics: Animals; Cell Line; Chromosome Aberrations; Coal; Cricetinae; Cricetulus; Dust; Humans; Lymphocytes; Lymphoma; Male; Mice; Mutation; Nitrites; Sister Chromatid Exchange; Sodium Nitrite

Topics: Carcinogens; Lymphoma; Nitrites; Sodium Nitrite; United States; United States Food and Drug Administration

Mice fed a diet containing 0.3 or 0.03% triethanolamine developed malignant tumors. Females showed a high incidence of tumors in lymphoid tissues, while this type was absent in males. Tumors in other tissues were produced at a considerable rate in both sexes, but no hepatoma was found. Triethanolamine was not mutagenic to Bacillus subtilis by itself, but it became mutagenic after reacting with sodium nitrite under acidic conditions or when the mixture was heated. Although N-nitrosodiethanolamine, a known carcinogen and mutagen, was detected in the reaction mixture by thin-layer chromatography, it may not be the main mutagenic product, because the product was a stable and direct mutagen and its mutagenic activity was destroyed by liver enzymes, unlike N-nitrosodiethanolamine. The lethal and mutagenic DNA damages produced by this unidentified product were susceptible to some extent to the repair functions of the bacteria.

Topics: Animals; Bacillus subtilis; Biotransformation; Carcinogens; Drug Interactions; Ethanolamines; Female; Lymphoma; Male; Mice; Mice, Inbred ICR; Mutagens; Neoplasms, Experimental; Nitrites; Sodium Nitrite