Hydrazines as mutagens in a histidine-requiring auxotroph of Salmonella typhimurium.

Hydrazines have been found naturally in tobacco and mushrooms. Other hydrazines are used in industry, medicine, and agriculture. Although about 38 hydrazines are carcinogenic, few, if any, have been tested successfully in rapid bacterial mutagenesis assays. We have utilized a tester strain of Salmonella typhimurium (TA1530) in order to determine the mutagenic activity of a number of hydrazines and related compounds. This strain is thus shown to be effective as a tester organism for the facile detection of hydrazines as mutagens.

Comparison of the metabolic profiles of benzo[alpha]pyrene obtained from primary cell cultures and subcellular fractions derived from normal and methylcholanthrene-induced rat liver.

Hepatocyte primary cell (HPC) cultures derived from either (a) non-induced (normal) or (b) methylcholanthrene (MC)-induced rat liver actively metabolized the carcinogen benzol[alpha]pyrene (BaP) over a 24-h period. In both cases, the BaP metabolites generated were qualitatively similar to those seen in the metabolism of BaP by isolated rat liver microsomal fractions; in addition, unidentified compounds were evident in the chromatographic profile generated by the cultured cells. In cells derived from (a), levels of known metabolites (phenols and diols) increased over the time period studied. On the other hand, in cells derived from (b), levels of diols decreased markedly after 8 h. These results suggest that induction with MC enhances both activation and, to a greater extent, conjugative-detoxification pathways of BaP, so that in cells obtained from (b) the formation of water-soluble metabolites is enhanced and levels of organic soluble metabolites are lower than in cells obtained from (a). Metabolism of BaP in primary cell culture derived from rat liver is thus seen to be similar to in vivo metabolism of the carcinogen, but somewhat in contrast to the in vitro microsomal (subcellular) metabolism of BaP where conjugative-detoxification pathways are virtually inoperative.

Effects of N-nitrosodiethanolamine and 1,1-diethanolhydrazine in Syrian golden hamsters.

N-Nitrosodiethanolamine (NDEA) and 1,1-diethanolhydrazine (DEH) were synthesized and injected subcutaneously weekly in male and female Syrian golden hamsters. The total NDEA dose per hamster was approx. 15 g/kg body wt. applied in either 7 or 27 subdoses. DEH was administered in 78 applications to two groups yielding total doses of 1.1 g and 273 mg/kg body wt. Under these conditions, DEH did not show a specific demonstrable carcinogenic effect. However, within 78 weeks after the first application, 39 out of 56 hamsters treated with NDEA developed tumors. Primarily, neoplasms of the nasal cavity and tracheal tumors were observed, as well as a few hepatocellular adenomas and sarcomas at the injection site. These findings and those of the earlier study on carcinogenicity of NDEA in rats raise concern as to the safety for human consumption or industrial use of products with the potential for forming NDEA.

Induction of tumors in mice with the herbicide succinic acid 2,2-dimethylhydrazide.

A solution of 2% succinic acid 2,2-dimethylhydrazide was given continuously in the drinking water of 6-week-old randomly bred albino mice for the remainder of their lives. The treatment gave rise to tumors of blood vessels, lungs, and kidneys. The tumor incidences in these tissues in the controls were 6, 18, and 0%, whereas in the treated groups the corresponding tumor incidences were 73, 73, and 5%. Light microscopic examination revealed typical angiomas and angiosarcomas of blood vessels, adenomas and adenocarcinomas of lungs, and adenomas of kidneys. The study thus demonstrates the tumorigenicity of the herbicide, succinic acid 2,2-dimethylhydrazide. Since the residues of this chemical occur in fruit, the human population is exposed to it. The environmental implication of this finding and the fact that the hydrazines as a class have tumorigenic properties are discussed.

Tumorigenic agents in unburned processed tobacco: N-nitrosodiethanolamine and 1,1-dimethylhydrazine.

Two tumorigenic agents, N-nitrosodiethanolamine and 1,1-dimethylhydrazine, have been isolated from tobacco for the first time. The former, a reportedly weak hepatic carcinogen in rats, varied in amounts from a low of 0.1 ppb in flue-cured tobacco not treated with the herbicide MH-30, to a high of 173 ppb in Burley tobacco to which the herbicide had been applied prior to harvesting. MH-30 (maleic hydrazide) used by farmers to remove 'suckers' from tobacco plants, is commonly formulated as the diethanolamine salt. 1,1-Dimethylhydrazine, reported to induce tumors in mice, ranged in amounts from 60 to 147 ppb, except in the case of Burley tobacco where none was detected (detection limit: 0.1 ng). The source of the nitrosamine in the tobacco appears to be the MH-30, whereas that of dimethylhydrazine has not been determined.

Cigarettes: chemical effects of sodium nitrate content.

Although addition of sodium nitrate to cigarettes is reported to reduce the components and properties of cigarette smoke that are associated with tumorigenicity, we find that the additive nevertheless significantly increases the levels of certain vapor-phase constituents of smoke that are known to inhibit ciliary movement; and also it produces other effects of questionable value.

Myristicin in cigarette smoke.

The pharmacologically active aromatic ether, myristicin, was isolated from the smoke of commercial cigarettes. The compound was identified by spectrometry (infrared, ultraviolet, and mass) and gas chromatography. The amount of myristicin in smoke is relatively low, and its contribution, if any, to the physiological action of cigarette smoke is unknowvn.