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At least 19 recordsLinked to original sources
PubMed1979

Can mutation theories of carcinogenesis set priorities for carcinogen testing programs?

The recent activity in designing, validating and implementing short-term tests for carcinogens has been spurred by the fairly convincing correlation between the carcinogenicity and mutagenicity of chemicals and by the assumption that mutations are somehow involved in neoplastic transformation. Moreover, it has been tacitly assumed that the mutagenic capacity alone of compounds would induce regulatory agencies to pass rules for their removal from man's environment, and would lead the public to avoid them. The actual response, however, is quite different. Government departments shy away from making any decisions on the basis of in vitro test systems, the public at large is becoming irritated by daily announcements that many of their cherished habits could adversely affect their health, and industries feel threatened and may reduce their search for new beneficial chemicals. The reluctance to accept wholeheartedly the mutagenicity tests for the detection of carcinogens is partly due to the uncertainty about the involvement of mutations in the formation of benign and malignant tumors. Following the initial rapid advances in the detection of environmental chemicals with carcinogenic and mutagenic properties, we seem to have arrived at the cross roads: we must now set new priorities for future research, and must make an unbiased assessment of the actual hazard of a compound to man and the human population.

Animals↗
PubMed1975

The activities of some polycyclic hydrocarbons and their "K region" epoxides in an in vitro-in vivo carcinogenicity test system.

Benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, dibenz(a)anthracene and benzo(a)pyrene and their related "K region" epoxides were tested for carcinogenic activities using a system in which mouse lung tissue was incubated in the presence of the test compound for 30 min and then implanted into isologous mice. Only 7,12-dimethylbenz(a)anthracene showed any marked carcinogenic activity under the conditions used, but all the compounds tested produced extensive proliferative outgrowths in the implanted tissues that may represent specific responses to the carcinogens.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1977

Selection of an in vitro carcinogenicity test for derivatives of the carcinogen hexamethylphosphoramide.

The demonstration that hexamethylphosphoramide (HMPA) possesses potent carcinogenic properties has raised doubts about the safety of exposure to other phosphoric amides. In order to define a suitable short-term test with which to evaluate such analogues, the response of the Salmonella typhimurium mutation assay of Ames and cell transformation assay of Styles to HMPA and 3 selected analogues has been studied. These analogues were the related leukaemogen phosphoramide, the putative non-carcinogen, phosphoric trianilide and N.N'N''-trimethylphosphorothioic triamide, a compound of unknown and hitherto unpredictable properties. While both tests found the trianilide negative, the Ames test failed to detect phosphoramide as positive and gave an erratic and predominantly negative response to HMPA. In contrast, the transformation assay found both phosphoramide and HMPA positive. This test response profile indicates that the transformation assay is the preferred test with which to evaluate analogues of HMPA for potential carcinogenicity. Some structural requirements for potential carcinogenicity within this class of compounds are tentatively deduced.

Anilides↗
PubMed1977

The activity of 7-methylbenz(a)anthracene metabolites in an in vitro-in vivo carcinogenicity test using mouse lung tissue.

7-Methylbenz(a)anthracene (7-MBA) and its 5,6-oxide and trans-5,6- and trans-8,9-dihydrodiol were tested for carcinogenic activity in a system in which mouse lung tissue was incubated in the presence of a test compound for 1 h and then implanted into isologous mice. All four compounds gave small yields of adenomas and in addition the 5,6-oxide gave two carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Mouse skin carcinogenicity tests of the flame retardants tris(2,3-dibromopropyl)phosphate, tetrakis(hydroxymethyl)phosphonium chloride, and polyvinyl bromide.

The flame retardants tris(2,3-dibromopropyl)phosphate, tetrakis(hydroxymethyl)phosphonium chloride, and polyvinyl bromide were tested for carcinogenic activity by skin application 3 times weekly in random-bred female ICR/Ha Swiss mice for 420 to 496 days. Tris(2,3-dibromopropyl)phosphate at two dose levels (30 mg and 10 mg/application) induced benign and malignant tumors of the skin, forestomach, and oral cavity (tongue and gingiva) in a statistically significant number of mice (30/group). A statistically significant incidence of papillary tumors of the lung was observed at both dosages, and the higher dose also resulted in one mouse with a tubular adenoma of the kidney. Tetrakis(hydroxymethyl)phosphonium chloride (2 mg/application, 60 mice) and polyvinyl bromide (0.1 ml latex suspension/application, 30 mice) were inactive. Polyvinyl bromide was also injected s.c. into another group of female ICR/Ha Swiss mice once weekly for 48 weeks, and the mice were observed for a total of 60 weeks. Liposarcomas were induced in 19 of 30 mice, which was ascribed to physical carcinogenesis. Appropriate solvent and no-treatment control groups were included.

Administration, Topical↗
PubMed1978

Relevance of short-term carcinogenicity tests to the study of the carcinogenic potential of urban air.

It is now accepted that screening for carcinogens in animals is expensive and demonstrates carcinogenic potential rather than actual carcinogenicity in man. A number of short-term tests which depend on mutagenicity, stimulation of DNA repair, ability to produce chromosome damage or other actions, and which correlate at least to some extent with carcinogenic potential, have been devised. These have the advantages of being rapid and cheap. Some can be carried out by using human cells. They may have advantages in the context of air pollution since they are sensitive down to very low dose levels and since they can deal with complex mixtures. Combinations of such tests may be of more value than any single test. Their particular value may be as a preliminary screening procedure in a tiered testing programme which may have high predictive efficiency.

Air Pollutants↗
PubMed1979

Carcinogenicity testing for control of environmental tumor development in man.

After briefly reviewing the present status of carcinogenicity testing as an aid to the control of environmental carcinogenesis in man, and discussing in somewhat more detail the relative advantages and limitations of animal testing and the two most widely used short-term assays--the Ames test and in vitro carcinogenesis--special attention is given to two points: 1) the difficulties inherent in extrapolating from the results of experimental tests an index of potential carcinogenic hazards in man; 2) the urgent need for additional testing procedures for the detection of associated factors (such as, cocarcinogenic factors and promoting agents) operating in human carcinogenesis.

Animals↗
PubMedDate not supplied

The role of metabolism of chemicals with respect to carcinogenicity tests.

Precarcinogens can be activated to carcinogenic effective compounds--ultimate carcinogens--by mammalian enzymes in vivo. In in vitro short-term tests, estimating effects which correlate with carcinogenicity in vivo of a chemical, these enzymes are represented by liver postmitochondrial fractions (S9) added to the test system. For the characterization and standardization of these S9 preparations we estimated certain enzymes involved in activating process: benzo(a)pyrene hydroxylase, the N-demethylases of dimethylnitrosamine, 4-dimethylaminoazobenzene and for a comparison, ethylmorphine as well as the azoreductase with 4-dimethylaminoazobenzene as a substrate. In order to get preparations with high enzyme activities, the animals such as rats, mice, hamsters and rabbits were pretreated by inducers such as polychlorinated biphenyls, phenobarbital, and 3-methylcholanthrene. We have observed species-specific differences in basic enzymatic patterns and in the degree of enzyme activities after induction. So it is principally possible to find out, whether or not a distinct animal species or strain is capable of metabolizing certain precarcinogens. Our aim is to optimize the evaluation of the carcinogenic risk of chemicals to humans by including human enzyme preparation in short-term tests.

2-Acetylaminofluorene↗
PubMed1978

Carcinogenicity testing of chemicals with particular reference to organochlorine pesticides.

The organochlorine chemicals comprise a large number of pesticides that are used widely throughout the world. The organochlorine pesticides given in the diet to mice are carcinogenic for the liver. They induce not only carcinomas of the liver, particularly at the higher doses, but also carcinomas and sarcomas in other organs in rats. They cause acute and chronic liver and kidney injury, which interferes with the development of carcinomas and sarcomas in rats. The testing of chemicals for carcinogenicity, with particular reference to organochlorine pesticides, includes discussions on the following topics: classification of hepatic lesions in mice and rats, toxicity versus carcinogenicity in the testing of chemicals, a comparison of carcinomas and cirrhosis of the liver in experimental animals and humans, and the significance of laboratory carcinogenicity findings to human health.

Adenoma, Bile Duct↗
PubMed1976

Carcinogenicity test of two unstaurated derivatives of N-nitrosopiperdine in Sprague-Dawley rats.

Two unsaturated derivatives of N-nitrosopiperidine (NP), N-nitroso-1,2,3,6-tetrahydropyridine (NTP) and N-nitrosoguvacoline (NGC), were administered to Sprague-Dawley rats as solutions in drinking water at concentrations equimolar (0.88X10(-3) M) with those used to test NP. NTP gave rise to hepatocellular tumors in contrast to the esophageal or olfactory tumors that were induced by NP. NGS did not induce tumors under these test conditions.

Animals↗