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D B Clayson

Publications and source records attributed to D B Clayson.

At least 55 records · Page 3Linked to original sources
PubMed1985

A 13-week feeding study of butylated hydroxyanisole: the subsequent regression of the induced lesions in male Fischer 344 rat forestomach epithelium.

Feeding butylated hydroxyanisole (BHA) to male Fischer 344 rats at concentrations of 2, 0.5, 0.25, 0.1 and 0% for 13 weeks led to proliferative lesions developing in the forestomach epithelium of the 2%-treated rats but not in other groups. The [methyl-3H]thymidine labelling index was raised in the 2%- and 0.5%-treated groups and showed an apparent no observable effect level at 0.25%. Within 1 week after withdrawal of BHA the labelling indexes in all treated groups returned to near the values in the controls. The induced mucosal lesions, however, reverted more slowly and even after 9 weeks on the basal diet, the stratified squamous epithelium along the lesser curvature, was still slightly thicker than the control. There were multilayered basal cell processes in the lamina propria with connections to the basal cell layer. The possible significance of these results to the ultimate development of cancer is discussed.

Animals↗
PubMed1985

An 85-day study of butylated hydroxyanisole in the cynomolgus monkey.

Groups of 8 cynomolgus monkeys (Macaca fascicularis) were given 500, 125 and 0 mg/kg body wt butylated hydroxyanisole (BHA) by gavage in corn oil 5 times/week for 20 days, after which the high dose was halved. No significant adverse clinical signs nor abnormal fibroscopic observations were noted before the experiment was terminated at 85 days. Blood levels of glucose, albumin, chloride, red blood cells (RBCs), hemoglobin (HGB), hematocrit (HCT) and mean corpuscular hemoglobin (MCH) were altered in a dose related manner but the altered values were well within normal ranges reported for this species. While histopathology showed no treatment related effects, the mitotic index was elevated 1.9-fold in the distal esophagus of monkeys in the high but not in the low dose group. Liver weights were increased in a dose related manner but liver monooxygenases, with the exception of decreased ethoxyresorufin deethylase activity, were all within normal limits. BHA given orally to monkeys at about the maximum tolerated dose failed to induce the massive changes noted with rats given 2% dietary BHA.

Animals↗
PubMed1985

Dose relationships in experimental carcinogenesis: dependence on multiple factors including biotransformation.

The probability of obtaining a tumor in a carcinogenesis bioassay depends mainly on the time on test and on the dose of carcinogen used. There is very limited data on the shape of this surface or reliable data on dose-response or time on test-response relationships. Ullrich's data on tumor induction by low dose radiation shows a variety of shapes of curve depending on the tissue chosen for investigation. As radiation probably does not concern the processes involved in xenobiotic metabolism, these observations clearly demonstrate that factors other than metabolism are important. An attempt is made to discuss the shape of the dose-response curve in relation to a number of factors including the background incidence of tumors in a tissue, mechanisms of "nongenotoxic" or toxicity-related carcinogenesis, and xenobiotic activation of carcinogens.

Animals↗
PubMed1984

Short-term pathological and proliferative effects of butylated hydroxyanisole and other phenolic antioxidants in the forestomach of Fischer 344 rats.

Food grade butylated hydroxyanisole (BHA) when incorporated in the diet and fed to male Fischer 344 rats for 9 or 27 days induced proliferative squamous epithelial changes in the lesser curvature of the forestomach proximate to the glandular stomach. These changes were assessed histopathologically and by [methyl-3H]thymidine radioautography. It was shown that BHA mixed dry into powdered diet, incorporated into the diet in corn oil, or in a pelleted diet, induced similar effects. When levels of 2%, 1%, 0.5%, 0.25%, 0.1% and 0% BHA were incorporated in rat diet for 9 days, the proliferative effect appeared to show a no effect level at 0.25% based on the [methyl-3H]thymidine-labelling index. Other food use antioxidants, namely butylated hydroxytoluene or tertiary butylhydroquinone, induced a lesser response than BHA at the maximum dose employed in the study. Propyl gallate was without effect. Propyl-4-hydroxybenzoate, a food use phenol, on the other hand, induced a less pronounced response than BHA but was more effective than the other antioxidants. Because increased cellular proliferation often provides an optimal milieu for tumor formation, it is suggested that these observations may be relevant to rat forestomach tumors induced by BHA.

Animals↗
PubMed1984

The mode of carcinogenic action of saccharin.

It is suggested that the induction of bladder cancer in male rats by saccharin is related to the integrity of the urothelial permeability barrier and that, in the Sprague-Dawley rat, saccharin is unable to attain a sufficient concentration in the urothelium if the barrier remains intact. The effect of saccharin, once it enters the urothelium, may be mediated by its ability to inhibit certain enzymes or by other mechanisms. The importance of the permeability barrier concept is explored as a means of identifying a human subpopulation possibly at an increased risk of saccharin-induced bladder cancer.

Animals↗
PubMed1983

The power and interpretation of the carcinogenicity bioassay.

Carcinogenicity is a major consideration in the assessment of risks due to environmental chemicals. The carcinogen bioassay therefore is a very important component of the battery of toxicological tests used in hazard evaluation. The strengths and limitations of this bioassay are discussed with emphasis upon the unresolved practical considerations, the interpretation of negative results, the significance of tumors induced in the presence of a high background incidence of naturally occurring tumors, and the difficulties in transspecies extrapolation. These factors, in combination with consideration of the biological mechanisms of chemical cancer induction, will be valuable in assessing the potential risk to man posed by individual chemicals.

Animals↗
PubMed1981

International Commission for Protection against Environmental Mutagens and Carcinogens. ICPEMC working paper 2/3: carcinogens and carcinogenesis enhancers.

The concept that chemical agents may lead to enhancement of carcinogenesis, rather than to its complete induction, is explored to explain the inexact correlation between carcinogen prescreening tests and the results of whole animal bioassays. It is suggested that carcinogenesis-enhancing agents are non-genotoxic chemicals which are positive in animal carcinogenesis bioassays. The importance of understanding the mechanisms of action of carcinogenesis-enhancing agents is emphasized.

Animals↗
PubMed1981

Specific aromatic amines as occupational bladder carcinogens.

The effect of specific aromatic amines in inducing bladder cancer among industrial workers exposed to these chemicals is documented. Most occupational bladder tumors are recognized to be due to 4 chemicals: 4-aminobiphenyl, 2-naphthylamine, benzidine, and commercial 1-naphthylamine that is contaminated with the 2-isomer. The consequences of this exposure are discussed.

Amines↗
PubMed1980

Comparison between in vitro and in vivo tests for carcinogenicity. An overview.

There are examples of short-term prescreening tests for carcinogenicity that fail to agree with the results of animal bioassays. Factors which may lead to such discordant results are discussed in terms of the present understanding of the mechanisms of chemical carcinogenesis and the quality of the results obtained in vivo and in vitro.

Animals↗
PubMed1979

NCI bioassays.

Explore the source record for details and available documents.

Animals↗
PubMed1979

Carcinogenic potential of hycanthone in mice and hamsters.

Hycanthone was administered to Schistosoma mansoni-infected and non-infected Syrian golden hamsters and Swiss mice by intraperitoneal and intramuscular injection of amounts up to the maximum tolerated dose. No tumors attributable to treatment were observed in hamsters. In infected mice, the overall incidence of hepatomas and hepatocellular carcinomas increased from 3.4% in untreated mice to 10.6% in those treated with hycanthone. Non-infected control mice developed 0.8% of these tumors compared to 10.2% in mice treated with hycanthone. Despite the use of high dose levels of hycanthone, statistical significance was attained only with non-infected female mice injected intraperitoneally and intramuscularly with hycanthone and then only at confidence levels of 92 and 95% respectively.

Animals↗
PubMed1979

Perinatal carcinogenesis: biologic curiosity or practical necessity?

Factors that require consideration in extending carcinogen bioassay protocols to include transplacental exposure of rodent subjects are summarized. These include metabolic complexities and biologic problems, such as the differences in fetal susceptibility to lethal, teratogenic, and carcinogenic effects of the same compound at different stages of intrauterine development, and that, with the present limited knowledge of transplacental carcinogenesis, transplacental and neonatal exposure to suspected carcinogens may lead to insoluble problems of interpretation. The view is expressed that agents to which the human fetus may be substantially exposed, including drugs and food additives, should nevertheless be tested for carcinogenicity by transplacental exposure.

Animals↗