Six short term tests for detecting carcinogenicity have been evaluated using 120 compounds, of which half were carcinogens and the rest non-carcinogens. The results obtained indicate that the Ames test and a "cell transformation" assay are both sufficiently sensitive to carcinogenicity, or the lack of it, in the compounds studied to enable them to be employed for detecting potential carcinogens. The consequences of using short term tests under various screening conditions have been explored. In order to have confidence in the results obtained for new or previously untested compounds it is important to use such tests in a carefully controlled manner.
Summary.-A number of tests have been described which are thought to be capable of identifying carcinogens without using the actual induction of cancer as an endpoint. This study compares the performance of 6 such tests on a selection of 120 organic chemicals. The tests studies were: (1) mutation of Salmonella typhimurium; (2) cell transformation; (3) degranulation of endoplasmic reticulum; (4) sebaceous gland suppression; (5) tetrazolium reduction and (6) subcutaneous implant. A further 4 tests were examined briefly, but were not included in the complete evaluation.The chemicals were classified into carcinogens (58) and non-carcinogens (62) on the basis of published experimental data, and into 1 of 4 broad chemical classes.There was considerable variation between tests in their ability to predict carcinogenicity, with the cell-transformation test and the bacterial-mutation test being the most accurate (94% and 93% accurate respectively). These 2 tests were considered to be of general use in screening, since they were clearly more accurate than the others. Statistical consideration of various combinations of these tests showed that the use of cell transformation and bacterial mutation together, provide an advantage over the use of either test alone. The inclusion of the other 4 tests in a screening battery predictably resulted in a great increase in overall inaccuracy and loss of discrimination, even though the detection of carcinogens is improved. All the tests were shown to generate both false positive and false negative results, a situation which may be controlled by the use, where possible, of appropriate chemical-class controls, to identify the test which is optimal for the class of chemical under test. Structural
Summary.-The effects of rat tumours of various macrophage contents on the syngeneic host's ability to produce either: (1) an inflammatory exudate in response to intraperitoneal oyster glycogen -or (2) a cutaneous delayed hypersensitivity (DHS) response to PPD or SRBC after appropriate sensitization, were studied as a function of tumour growth.Both these reactions were found to be markedly decreased as the tumours grew. The suppression was greatest in animals bearing tumours of high macrophage content. The suppression of the DHS response could be reversed by a local injection of normal peritoneal macrophages with the eliciting antigen, and lymphocytes from tumour bearing animals exhibiting poor DHS responses were able to adoptively transfer DHS reactivity to normal unsensitized recipients. The monocyte infiltration in response to oyster glycogen was also decreased, and these data indicate a monocyte, rather than a lymphocyte defect in the tumour induced " anergy " in this system.
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