A toxicity method with calcium cyclamate for chronic carcinogenesis experiments.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to B Toth.
Explore the source record for details and available documents.
Capsaicin, the pungent principle of hot pepper, was administered at concentrations of 1, 0.5, 0.25, 0.125 and 0.0625% in powdered diet for 35 days to five groups of Swiss albino mice. In the capsaicin-treated groups 4 mice (10%) developed 4 adenocarcinomas of the duodenum (one tumor at each dose level, except for the highest dose), while no such tumor occurred in the untreated control mice. Capsaicin exhibited a low level of mutagenicity in the Ames assay with S. typhimurium strain TA98 in the presence of liver activating enzymes from Aroclor-induced rats.
1,2-Dimethylhydrazine dihydrochloride (1,2-DMH) was given to Swiss mice in 1 or 10 weekly intracolonic instillations of 60 and 40 micrograms/g body weight, respectively. In mice that received a single treatment, the tumor incidences in the lungs, blood vessels and subcutis were 34% (p less than 0.006), 8 and 25 in females and 2, 20 and 0% in males, respectively. In mice treated repeatedly with the carcinogen, the corresponding tumor incidences were 34% (p less than 0.006), 38% (p less than 0.000001) and 12% (p less than 0.03) in females and 34, 10 and 0% in males, respectively. In control mice the tumor incidences in lungs, blood vessels and subcutis were 15, 8 and 2% in females and 22, 5 and 2% in males, respectively. The induction of large intestinal cancer, which was the main objective of this investigation, however, failed to materialize.
Explore the source record for details and available documents.
A dose response study in carcinogenesis by 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) in Swiss mice was performed. The compound was administered continuously in drinking water for life from 6 weeks of age at dose levels of 0.002, 0.001, 0.0005, 0.00025, 0.000125, 0.0000625, 0.00003125 and 0.000015625%. A positive correlation was established between the dose levels of 1,2-DMH and the yield of blood vessel tumors. In addition, the latency periods for these tumors diminished when the dose levels of the carcinogen decreased. Although some of the treatments induced lung tumors, no association was observed between the dose levels of the carcinogen and the lung tumor incidence. The study thus provides an example in which the continuous lifespan administration of a carcinogen resulted in a partial dose response effect. This method of administration closely resembles some of the human exposure situation.
A comparative assessment is performed on one of the false morel mushrooms, Gyromitra esculenta, including the amounts of some hydrazines present in this fungus, the cancer-inducing doses of these chemicals or the mushroom used in animal experiments, the total amounts of the hydrazines or mushroom needed to induce neoplasms in mice and the estimated total amounts of hydrazines or mushroom needed to induce cancer in humans. When one compares the estimated amounts of hydrazines required to induce cancer with the amount of raw Gyromitra esculenta needed to yield a similar effect, it becomes clear that to date 37 percent of the carcinogenic ingredients of this fungus have been identified.
The review summarizes the results of 30 hydrazines, which were studied in humans and in six animal species for teratogenic activities. Of these, 23 chemicals were found to induce physical defects in the developing embryos of animals. Six hydrazines failed to induce teratogenic abnormalities in animals under the experimental conditions. Three hydrazine analogues, some of which were given in combination with other drugs to pregnant women, gave ambiguous results concerning teratogenic effects. Some of these investigations were aimed at revealing the teratogenic mode of action of hydrazines. The mechanistic aspect focused on the dose requirements of chemicals and the time period in the development of the fetus susceptible to malformation and chemoprevention. Of interest is the base compound hydrazine, which was found to be teratogenic in five animal species. In general, the hydrazines were found to be powerful teratogens, which coincided in most cases with their known carcinogenic activities.
The antineoplastic activities of hydrazines and hydrazine-containing natural products are summarized and reviewed. Many of these, including the base compound hydrazine, some of its 79 analogues and 2 hydrazine-containing cultivated mushrooms, exhibited antineoplastic actions in animals and some of them in humans. In addition, a substantial number of hydrazine analogues were further derivatized (altogether 331 derivatives were prepared) and studied to a limited extent for cancer chemotherapeutic activity in animals. Subsequently, only one hydrazine, N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide HCl (procarbazine, natulan) was used extensively in human medicine. Because this drug is a highly carcinogenic substance in animals and since a substantial amount of evidence points to the possibility that it is co-carcinogenic or carcinogenic itself in humans, its use has largely been abandoned. Because well over 80% of the studied hydrazine class of compounds are carcinogenic, therefore, it may not be rewarding to search among them for cancer cure.
Agaricus bisporus, the cultivated mushroom of the western hemisphere, was baked at 220-230 degrees C for 10 minutes and subsequently fed to mice for 12 hours each day, five days each week throughout their life. After each feeding cycle, the animals received a well-balanced semisynthetic diet for 12 hours each day for five days plus the remaining two full days each week. The estimated average daily mushroom consumption per animal was 4.8 g for a female and 4.2 g for a male. Randomly bred Swiss mice, six weeks old at the start of the experiment, were used. In the baked mushroom-fed group, the incidences of tumors in the lungs, blood vessels, cecum, and colon increased when compared to the untreated controls. These increases were not, however, statistically significant. In another previous experiment, both the raw and the baked mushrooms, when used in different feeding regimens, induced statistically significant incidences of cancers in several organs of the mice. It is possible that the negative finding in the current study was due to insufficient mushroom consumption.
Continuous administration of 10, 5, and 2.5% lyophilized Agaricus bisporus (AB) mushroom in the diet of six-week-old, randomly bred Swiss mice for life induced tumors in the lungs, forestomach, glandular stomach, and ovaries in certain groups. Some of the tumor incidences were found to be statistically significant, although no dose-response relationship was established. Histopathologically, the neoplasms were classified as adenomas and adenocarcinomas of lungs, glandular stomach, and ovaries and squamous cell papillomas and carcinomas of the forestomach. AB given in both raw and baked forms induced tumors in the same species in earlier experiments. Since this fungus is consumed in lyophilized form to a certain degree in the United States, the results may carry practical significance.
Benzenediazonium sulfate (BD) was given to Swiss mice by 26 subcutaneous injections of 10 micrograms/g body weight at weekly intervals. The treatment gave rise to tumors of the subcutis. The tumor incidences in the treated groups were 42% in females and 26% in males. The corresponding tumor incidences in the untreated controls were 0% in females and 2% in males. Histopathologically, the neoplasms were classified as fibrosarcomas, rhabdomyosarcomas, and osteosarcomas of the subcutaneous tissue. BD is formed during the cytochrome P-450 catalyzed metabolism of the carcinogenic 1-(phenylazo)-2-hydroxynaphthalene (Sudan I, Solvent Yellow 14), which was used as a coloring agent for food and other materials in several countries. Further, BD is a metabolic breakdown product of different classes of nitrogen-nitrogen bond- containing chemicals. BD is the fourth benzenediazonium salt found to be carcinogenic in this laboratory.