Carcinogenesis; a comprehensive survey最新文献

The 1982 Report of the Surgeon General of the U.S. Public Health Service concluded that "cigarette smoking is the major single cause of cancer mortality in the United States" and that "85 percent of lung cancer cases are due to smoking". Thus, major emphasis should be placed on school health education programs designed to prevent young people from smoking. Those students who are already cigarette smokers should be provided with an opportunity to attend smoking cessation courses with the hope that they stop. However, as long as society condones tobacco usage, millions of people will smoke, and millions of others will be involuntarily exposed to tobacco smoke. In this communication we have discussed the need for future research on the etiology of lung cancer. This includes the observation of a shift toward an increasing proportion of adenocarcinoma compared to squamous cell carcinoma of the lung in men, more detailed knowledge of the effects of macro- and micronutrients in the etiology of lung cancer, a clear delineation of the impact of tumor initiators, tumor promoters, and cocarcinogens in the development of lung cancer in cigarette smokers, and a study of the effects of the low-yield cigarette on the lung cancer risk of smokers. Finally, we reviewed the present knowledge as to the possible association of passive smoke exposure and lung cancer. Here we have placed major emphasis on the need for a close cooperation between epidemiologists and clinical biochemists in risk assessment.

The transformation of C3H/10T1/2 cells can be made to proceed through discrete stages of initiation and promotion. Studies of the effect of cell density upon focus formation in cultures treated with MNNG and TPA suggest that initiation by MNNG is due to a relatively infrequent, irreversible event induced by a single carcinogen treatment. In contrast, promotion appears to be a reversible process requiring multiple treatments with TPA over a protracted period of time. Some evidence suggests that promotion may entail the induction of phenotypic changes which impart a growth advantage to phenotypically unstable "initiated" cell populations. The actual cellular mechanism(s) for most of the phenomena observed in C3H/10T1/2 cultures have eluded precise definition and widely divergent hypotheses have been advanced to explain transformation, initiation, and promotion. Conceivably there are multiple mechanisms responsible for each of these phenomenon. Some agents may transform by a multistage mechanism whereas others may exert their effects in a more direct fashion. Some of the foci produced by promotion may be the result of simple selective processes, others the product of more complex inductive events. Variations would thus be expected between laboratories working with different protocols and agents. As demonstrated by the possible involvement of an MCA residue in transformation, it is also apparent that fundamental technical aspects of this conceptually simple cell transformation system are poorly understood. While it is natural to develop mechanistic models based on quantitative observations of transformation, a limited understanding of the basic cell culture variables which modulate both the induction and expression of transformation dictate that caution be exercised in extrapolating the significance of such models to in vivo carcinogenesis.

One cellular transformation assay system (Syrian hamster embryo (SHE) primary cells) and two viral mediated transformation systems (primary Syrian hamster embryo cells infected with Simian adenovirus type 7 (SHE/SA7), and a rat fibroblast cell line (2FR450) infected with Rauscher leukemia virus (Rat/RLV] were evaluated using a group of nine "model" and five coded chemicals. The purpose of the project was to establish the intra- and interlaboratory reproducibility of the assays and to provide a basis for objective comparisons between the systems. This is a preliminary evaluation of the assay systems using the results for these chemicals tested in eight collaborating laboratories under the auspices of the National Toxicology Program (NTP). The endpoint measured in each system is very different and a positive response in each had to be separately defined. The assay systems all produced a response to carcinogens and in most instances the responses could be qualitatively reproduced in the different laboratories. However, the assays differed significantly in their ability to demonstrate dose-related effects. In addition, multiple tests or modified assay procedures were required with every system in order to insure that chemicals had been adequately tested. In each system, technical or procedural limitations exist that preclude the application of these assays to routine chemical testing at this time. Among these limitations were ambiguity in scoring morphological transformation, significant but poorly defined influence of reagents such as serum or metabolic activation systems on test performance, and difficulty in repeating responses to a given chemical. Additional efforts to overcome these limitations will be necessary in order to make these test systems of use in routine testing of unknown chemicals for genetic toxicity.