Biomedical subjects
Publications and source records attributed to G B Pliss.
The costs of labor, equipment (wear and tear included), animals' upkeep, running costs, etc. involved in chronic tests of chemical agents for potential carcinogenicity conducted at the Institute totaled 16,998 Rbs. The structure of the expenditure is discussed.
The approaches to prepare a uniform and unified scientific terminology of chemical carcinogenesis are presented. The main definitions proposed (carcinogen, initiation, promotion, mutagen, multistage carcinogenesis, anti-carcinogen, cocarcinogen, carcinogenic risk, etc.) are based on the current state of comprehending mechanisms of the action of chemical carcinogens.
A glossary of terms related to chemical carcinogenesis is presented. The definitions proposed are based on the current state of understanding mechanisms of the action of chemical carcinogens.
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The skin of white outbred rats was painted with solutions of N-methyl-N-nitrosourea (MNU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N,N'-dinitroguanidine and diazoacetic ester (DAAE). DAAE was administered to rats intravenously, intraperitoneally and subcutaneously as well. Skin tumours have appeared only in the experiments with MNU, MNNG and DAAE. The application of MNU and MNNG caused tumours of the skin in the site of application, and as for DAAE, it induced tumours in the remote places of the skin. Systemic methods of DAAE administration entailed mainly mammary tumours in female rats, but not those of the skin. Possible mechanisms of action of the compounds under study have been discussed.
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Six aromatic amines were studied for their mutagenic activity using Salmonella typhimurium TA 100 and TA 98. 3,3'-dichlorobenzidine, ortho-tolidine, benzidine, 2-naphthylamine proved to be mutagenic, while aminotobias acid and 2,2',4,4'-tetraaminodiphenyl did not show mutagenic activity. Chronic experiments on mice and rats using these compounds revealed a close correlation between carcinogenicity and mutagenicity.
Solution of N-methyl-N-nitrosourea (MNU), diazoacetic ester (DAAE), N-methyl-N-nitro-N-nitrosoguanidine (MNNG), N-methyl-N,N'-dinitroguanidine, 4-dimethylaminoazobenzene (DAB), o-aminoazotoluene or 7,12-dimethylbenz(a)anthracene (DMBA) were applied to rat skin. Neoplasms (skin tumors) were found only in the experiments with MNU, DAAE, MNNG, DAB and DMBA, MNU, MNNG, DAB and DMBA induced tumours in the sites of skin painting. In experiments with DAAE distant skin neoplasms developed as well. Possible mechanisms of action of these compounds are discussed.
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An 0.5% acetone solution of 7,12-dimethylbenz(a) anthracene was applied to the mucosa of the cheek pouch of 68 Syrian male hamsters. Cytological examination of mucosa samples obtained from the cheek pouch was carried out, and the bioptates and tissues of dead animals were studied histologically. Squamous cell carcinoma of the pouch was identified in 100%. Cytologically-confirmed hyperplasia and dysplasia of the epithelium were found to precede cancer development.
The oncologic and non-oncologic morbidity in intact CC57BR mice was studied over a period of 1978-1980. Tumors occurred in 23.5%, while malignant tumors were in 14.3% of mice. Benign adenomas of lung were the most frequent 10.9%. Malignant tumors included generalized reticulosarcomatosis and leukemia 6.8%, cancer of the skin 3.4% and single different tumors. Pneumonia and enteritis were the most frequent among non-oncologic diseases. Since CC57BR mice belong to a low cancer line, they should be used for various long-term cancer and non-cancer experiments.
Treatment with 2-naphthylamine was followed by an 1.5-3 fold increase in the frequency of hyperplastic changes in the organ culture cells of rat urinary bladder epithelium, as compared with intact control and cell cultures treated with a non-carcinogenic analog (30.8, 17.6 and 10.7%, respectively). It is suggested that this effect was associated with the initial specific blastogenic effect of 2-naphthylamine metabolites on rat urothelium, the latter being traditionally considered resistant to this agent. Some other factors absent in rats but present in humans and dogs are indispensable for further malignant transformation and tumorigenesis.
To the cheek pouch mucosa of 118 male Syrian golden hamsters 0.5% acetone solution of 7,12-dimethylbenz (a) anthracene was applied 3 times a week during 2 months. Two months after beginning of the experiments all the hamsters developed tumors. Since that time a mixture of epidermal G1 and G2 chalones was applied to the cheek pouch mucosa of the experimental animals 5 times a week. The control hamsters received saline alone. As compared to the control, the experimental hamsters demonstrated an increase in the life-span, tumor growth retardation and regression of part of the tumors. The data obtained attest to the anti-neoplastic action of chalones.
Carcinogenic action of dimethylnitramine (DMNO), diethylnitramine (DENO), and dibuthylnitramine (DBNO) on various animal species was studied. 200 ppm of DMNO in tap water induced no tumours in outbred rats, while DBNO induced hyperplastic lesions on the urinary bladder and DENO produced liver tumours in 2 of 5 rats. DMNO dissolve in aquarium water at a dose of 5 ppm induced tumours (kidney and liver adenocarcinomas and hemocytoblastosis) in 18 out of 40 and 6 out of 18 frogs respectively. Another amphibian species, Xenopus, showed similar sensitivity to DMNO action: hepatocellular cancers, cholangiocarcinomas and kidney tumours were found in 6 out of 14 animals and in another group, in 6 out of 17 animals treated with 400 ppm of DMNO dissolved in aquarium water. Few neoplasms were observed in experiments on fish (guppies zebrafish) and freshwater mollusks treated with DMNO and DENO. The carcinogenic effect of nitramines, appears to be much lower than that of related nitrosamines.
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