Theory and practice of primary cancer prevention

Abstract

The primary aim of cancer prevention is to stop carcinogens from entering the body. Since the low doses involved in carcinogenesis do not cause true toxicological effects, usual toxicological analytic methods do not allow the detection of the early effects of carcinogens. Exposure to chemical carcinogens causes damage to nuclear chromatin, the most vulnerable part of the cell, by inducing DNA damage, chromosomal abnormalities and mutations, which foreshadow the danger of cancer development. In such cases intervention is possible in two ways. On the one hand, we attempt to remove the causative agent from the environment, while on the other we aid the elimination of somatic mutations. The latter is called active prevention; the introduction of substances into the body that can help the elimination of defective cells (apoptosis induction) or stop processes responsible for elongation errors (i.e. with antioxidants). Concerning our own studies, we present the results of 25 years of research on the genotoxicological characteristics of workers exposed to various chemicals, which show that active prevention can in fact be effective in conjunction with information on specific biomarkers. We present in detail the genotoxic changes found in hospital nurses who routinely administer intravenous cytostatic therapy, and the relationship of these changes to their immunotoxic and clinical laboratory parameters. Genotoxic substances decrease the oxidative burst and natural killer (NK) cell activity, which may explain the immunosuppressive effects of occupational exposures. We also present the detailed results of a follow-up study involving two groups of industrial workers. We monitored the status of workers involved in benzene production for 15 years and of asphalt industry workers for 8 years. In both studies we concluded that genotoxic effects can be decreased by ensuring appropriate working conditions, while a temporary lapse in these conditions or accidental changes lead to increases in genotoxic parameters. Since genotoxic effects develop over an extended period (4-5 months), they are independent of hygienic conditions at any single inspection and, thus, their detection also offers a way to ascertain true exposure levels. Our studies also show a connection between genotoxic effects and immune function, which is adversely affected not only by occupational exposures, but also by medications and smoking. From our results with workers in the oil and asphalt industries, we concluded that the levels of chromosomal aberrations (CAs) and sister chromatid exchange (SCE) increase in proportion to exposure levels and decrease with a certain delay following the attenuation of the exposure. We could not detect an increased frequency of any chronic disease in industrial workers. The increased numbers of iron deficiency anemia and thyroid disease in nurses providing cytostatic therapy was, however, related to their occupational exposure.