Showing papers by "Eppley Institute for Research in Cancer and Allied Diseases published in 1983"

Enhancing effect of vitamin E on murine intestinal tumorigenesis by 1,2-dimethylhydrazine dihydrochloride.

Abstract: The effect of the antioxidant vitamin E on the tumor-inducing ability of 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) was investigated in randomly bred Swiss mice. Three groups of mice that were 6 weeks of age at the beginning of the experiment received the following treatments: a) vitamin E acetate [DL-alpha-tocopheryl acetate (TA)] at a 4% dose level in a powdered diet for life; b) 1,2-DMH, 10 weekly sc injections at 20 micrograms/g body weight; c) combination of a and b treatments. The administration of TA enhanced the tumorigenicity of 1,2-DMH, as evidenced by statistically significant incidences of tumors in the duodenum, cecum, colon, rectum, and anus. The present finding apparently is in contrast with the reported inhibitory effect of TA on colon carcinogenesis by 1,2-DMH.

Infection of Normal Human Epithelial Cells by Epstein-Barr Virus

Abstract: Primary cultures of epithelial cells were grown from the tonsils and adenoids of patients with diseases not related to Epstein-Barr virus. The cells could not be infected by Epstein-Barr virus. Fluorescein-labeled Epstein-Barr virus and a cytofluorograph were then used to show that the epithelial cells do not have detectable receptors for the virus. However, implantation with Epstein-Barr virus receptors gave the cells the ability to bind the labeled virus. One to 5 percent of receptor-implanted cells exposed to the transforming B95-8 substrain of the virus expressed Epstein-Barr nuclear antigen. The early and viral capsid Epstein-Barr virus-determined antigens were not detected in the virus-infected cultures. The results show that normal human epithelial cells from the nasopharynx become susceptible to infection by Epstein-Barr virus when the membrane barrier resulting from the lack of viral receptors is overcome by receptor implantation.

Prostatic cancer induced in MRC rats by N-nitrosobis(2-oxopropyl)-amine and N-nitrosobis(2-hydroxypropyl)amine.

Abstract: Weekly intragastric treatment with N-nitrosobis(2-oxopropyl)amine or N-nitrosobis(2-hydroxypropyl)amine induced hyperplastic, preneoplastic and neoplastic prostatic changes in greater than 80% of MRC rats. The lesions initially appeared as focal or multifocal proliferations of alveolar epithelium in a cribriform pattern which, in all but one case, underwent progressive changes, often tending toward squamous cell formation. Tumors, found primarily in the ventral prostate, demonstrated various degrees of differentiation and invasive growth. A few neoplasms developed in the seminal vesicles; however all were of a glandular type. The sequential alteration of induced lesions is described and the possible reasons for the squamous cell character of most tumors discussed. Prostatic cancer induction by systemic application of specific nitrosamines could provide a unique tool for investigating important aspects of the disease.

Increased Tumorigenesis Induced byN-Nitrosobis(2-oxopropyl)amine in Syrian Golden Hamsters Fed High-Fat Diets1.

Abstract: The effects of dietary fat on carcinogenesis were presented, with the pancreas excluded, in randombred Syrian golden hamsters after administration of N-nitrosobis(2-oxopropyl)amine (BOP). Diets containing 4.5, 9, or 18 g corn oil/385 kilocalories [low-fat (LF), medium-fat (MF), or high-fat (HF) diet, respectively] were fed in two sequences. In the first sequence during which the effects of fat on the initiation phase of BOP carcinogenicity were examined, LF or HF diets were fed to hamsters 3-7 weeks of age and for 2 days after a single sc BOP treatment (10 mg/kg body wt) to 8-week-old hamsters. These hamsters were then given MF diet for the remainder of their lives. In the second sequence during which the role of fat on the promotional phase (development) of BOP-induced cancer was evaluated, MF diet was fed during the weeks preceding BOP treatment and LF or HF levels were given after BOP treatment. Separate groups were fed MF diet throughout both phases, and parallel animal groups received each diet sequence and were treated with saline at 8 weeks of age. Renal adenocarcinomas in males were observed only in those given HF diet either before or after BOP treatment (9% incidence). Similarly, pulmonary adenoma and intraphepatic biliary cystic adenoma (cholangioma) incidences were elevated above spontaneous rates in HF-fed groups. This study demonstrated that dietary fat enhanced BOP-induced tumorigenesis in the kidneys, lungs, and liver when fed, either during initiation (preceding carcinogen treatment) or at promotional stages (following carcinogen treatment).

Trans-Species and Trans-Tissue Extrapolation of Carcinogenicity Assays

Abstract: From earliest times, mankind has endowed animals with specific human attributes. Language reflects many of these attributes in phrases such as “wise as an owl,” “cunning as a fox,” or “assinine.” Soothsayers have used the detailed morphological examination of outbred animals to predict man’s fate in the future. It is relevant to our present society that none of these attributions were scientific absolutes; they could be manipulated to suit the current political exigencies. Our current mysticism dictates that we regard all agents that induce cancer in animals as having the same effect in man. Although some evidence for this theory exists, and it represents a cautious view, it is again by no means a scientific absolute.

In vitro screening of the effect of hydrazine derivatives on hepatic aryl hydrocarbon hydroxylase activity

Abstract: 1. The effect of hydrazine derivatives on the in vitro hepatic microsomal aryl hydrocarbon hydroxylase activity was examined using Sprague-Dawley male rats. 2. All hydrazine derivatives examined have some degree of inhibition on hepatic aryl hydrocarbon hydroxylase activity. 3. The inhibitory effect is concentration dependent and is also dependent on the structural substitution of the hydrazines. The more lipophilic the derivative, the more potent the inhibition of aryl hydrocarbon hydroxylase activity.