Autoradiographic studies on the incorporation of heterologous DNA into the Novikoff hepatoma cells.
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The study was concerned with objective criteria for identification of actual carcinogenic hazards. It used quantitative analysis data on morphologic structures of tumors induced in 12565 albino noninbred rats in the course of carcinogenicity evaluation of 112 chemical agents. The totality of all the data were analyzed versus morphologic parameters of tumors and carcinogenicity of the agents. Spontaneous tumors turned to be the cause of death in animals treated with noncarcinogenic or slightly carcinogenic agents whereas a completely different spectrum of tumors were responsible for lethality in those receiving potent carcinogens. It was inferred that increased incidence of spontaneous tumors following treatment with maximum tolerable doses can not be used as a criterion of actual blastogenicity of an agent.
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Two studies on the carcinogenicity of the fungicide captan in animals were reviewed. The results and conclusions, which were based on my examination of the histological sections, showed that captan is highly carcinogenic in rats and mice. Neoplasms at all sites, as well as malignant neoplasms, were increased in both low and high dose captan-treated male and female rats. Benign and malignant neoplasms of the endocrine organs were increased in low and high dose male and female rats ingesting captan. Neoplasms of the adrenal and pituitary glands were increased. Increased incidences of benign and malignant neoplasms, and of malignant neoplasms only, were observed in the reproductive system of female rats ingesting captan. The incidence of these neoplasms was markedly increased in the mammary gland and ovary. Female rats given captan were more susceptible to the development of hepatic neoplasms than were male rats. Captan induced neoplasms of the duodenum in male and female mice. There also were toxic changes in rats. Captan-treated male rats were more susceptible to the induction of chronic renal disease than were female rats. Male rats also had a high incidence of particularly severe testicular atrophy as a result of the ingestion of captan. Such lesions interfere with the health of the rats and with the development of neoplasms.
Transplacental treatment with synestrol exerted a slight modifying effect on nitrosoethylurea-induced carcinogenesis in random-bred albino rats: prenatal treatment with synestrol reduced the rates of Leydig-cell and uterine tumor incidence to those of spontaneous tumors.
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Intrapleural growth of transplanted rat tumours was prevented or retarded by intrapleural administration of double-stranded RNA. A similar suppression of growth was achieved with peitoneal tumours by the intraperitoneal injection of the compound. These studies indicate the possible potential of this form of treatment of thoracic and peritoneal tumours for clinical application in the treatment of mesothelioma.
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Experiments in animals have shown that high-fat diets can enhance tumor growth. Animals receiving high-fat diets routinely ingest up to 5 times the level of fat (by weight) found in standard chow diets. Rats given oil by gavage can triple caloric intake from fat compared to untreated controls. In laboratory animals, high-fat diets appear to play a role during the postinitiation phase of tumorigenesis. The type, level, and nature of the dietary fat may also affect the outcome of bioassays. Fat does not initiate the tumorigenic process. Additional factors must be considered when studying and interpreting the effects of dietary fat. Animal diets and dietary fats should be protected against oxidation. Antioxidants protect against oxidation but may also modify the tumorigenic process. Adequate levels of essential fatty acids must be provided. Dietary fat level can alter nutrient density and palatability; each of these factors can affect nutrient intake which can in turn influence metabolic processes.
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