Biomedical subjects
Publications and source records attributed to J Althoff.
Chronic administration of saccharin and sodium or calcium cyclamates in drinking water to Syrian golden hamsters, up the maximum tolerated dose level, failed to induce an excess of tumors compared to controls; nor were any urinary bladder tumors found.
2, 2-Dihydroxy-di-n-propylnitrosamine (DHPN), an assumed metabolite of di-n-propylnitrosamine (DPN), injected subcutaneously once weekly for life, was carcinogenic in Syrian hamsters. The main target organs were the respiratory tract, pancreas, liver, and kidneys. In the respiratory system the most affected segments were the nasal cavities and the lungs. Adenomas and adenocarcinomas, mostly of ductal origin, were induced in the pancreas. Liver neoplasms were hemangloendotheliomas, angiosarcomas, hepatocellular adenomas, cholangiomas, and cholangiocarcinomas. Kidney neoplasms were adenomas and adenocarcinomas. The morphology of the induced neoplasms was described, as well as the effects of DHPN, compared to those another possible metabolite of DPN, 2-hydroxypropyl-n-propylnitrosamine (2-HPPN), which is formed in vivo with only 1 aliphatic chain degraded via theta-oxidation.
Oxidation at the beta carbon occurred in metabolism of di-n-propylnitrosamine (DPN), previously shown to be carcinogenic for animals. When 2,2'-dimethyldipropylnitrosamine (DMDPN) was injected sc once a week for life into male and female Syrian hamsters at levels of 500, 250, 125, and 62.5 mg/kg body weight, it induced neoplasms in the nasal cavities, larynx, trachea, and stem bronchi. Since the presence of a methyl group on the beta carbon suggested that DMDPN could not undergo beta oxidation, the carcinogenicity of DPN for these portions of the respiratory tract was probably unrelated to beta oxidation, though earlier experiments had indicated the possibility of this mechanism. Because DMDPN failed to induce neoplasms in other organs, the carcinogenicity of DPN or its beta metabolites for the lungs, liver, pancreas, and kidneys was not explained by this experiment.
Weekly s.c. injections of equitoxic doses of 2-hydroxy-propyl-n-propylnitrosamine, 2-oxopropyl-n-propylnitrosamine, and methyl-n-propylnitrosamine, assumed metabolites of di-n-propylnitrosamine by beta oxidation, induced low incidences of pancreatic duct adenomas in Syrian golden hamsters. Di-n-propylnitrosamine did not. Application of 2,2'-dihydroxydi-n-propylnitrosamine, another postulated intermediate of di-n-propylnitrosamine, led to development of various types of pancreatic duct adenomas and ductal carcinomas in high percentages of hamsters. In addition, a few acinar-cell carcinomas were found. The morphology of these neoplasms, their latencies, and their distribution in the different segments of the pancreas are described.
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A high incidence of pancreatic neoplasms was induced in Syrian golden hamsters following subcutaneous applications of diisopropanolnitrosamine (DIPN) once weekly for life. The tumor latency was as short as 15 weeks. In clinical and morphologic aspects the induced pancreatic tumors closely resembled those of humans.
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