Biochemical and molecular epidemiology of human cancer: indicators of carcinogen exposure, DNA damage, and genetic predisposition.

The primary goal of biochemical and molecular epidemiology is to identify individuals at high cancer risk by obtaining evidence of high exposure to carcinogens, leading to pathobiological lesions in target cells, and/or increased oncogenic susceptibility due to either inherited or acquired host factors. This emerging and multidisciplinary area of cancer research combines epidemiological and laboratory approaches. Because DNA is considered to be an important target for modification by mutagens and carcinogens, damage to DNA can be used as an internal, molecular dosimeter of carcinogen exposure. The reactive species of these carcinogens may directly bind to DNA to form adducts and may indirectly cause secondary DNA lesions, e.g., via induction of free radicals and aldehydes. Highly sensitive and specific methods have been developed to measure the minute amounts of DNA lesions and DNA repair products found in biological specimens from humans exposed to carcinogens. For example, DNA adducts have been measured in cells and tissues from people occupationally exposed to carcinogenic polycyclic aromatic hydrocarbons. Antibodies recognizing carcinogen-DNA adducts have also been detected in human sera. Inherited predisposition to cancer has been revealed by recent advances in molecular genetics, including restriction-fragment-length polymorphism. For example, the hypothesis that rare alleles of the Ha-ras proto-oncogene are associated with an increased risk of lung cancer is currently being tested. These approaches afford the potential of biochemical and molecular epidemiology to predict disease risk for individual persons, instead of for populations, and before the onset of clinically evident disease.

Cancer mortality among workers in a thermoelectric power plant.

At a thermoelectric power plant in Turbigo (Milan, Italy), an analysis of the technological process has shown the presence of exposure to several carcinogens: polycyclic aromatic hydrocarbons, asbestos, hydrazine, polychlorinated biphenyls, chromium, nickel, and beryllium. An epidemiologic study was carried out to quantify the effect of the detected exposures on the workers, and the cancer mortality of the cohort was compared with the corresponding rates from the closest town and with cancer register data from a nearby province. Excess mortality was found for workers with 10 or more years of employment; the median latency time was about 20 years.

[Immune reactions in malnutrition and aflatoxin blastomogenesis]. / Immunnye reaktsii pri neopolnotsennom pitanii i aflatoksinovom blastomogeneze.

Experiments were made on 80 male Wistar rats kept for 210 days on the common (respectively restricted protein) diet and exposed to aflatoxin intoxication. Humoral immunity was elucidated by qualitative and semi-quantitative immunoelectrophoretic analysis of the IgG and IgM levels, as was the presence of circulating autoantibodies in the test animals' serum. At the end of the experiments the development of leiomyosarcomas was noted in the absence of primary neoplastic transformation in the liver. The tumors were less incident in the animals kept on the low-grade diet than in those kept on the full-value diet. Immunoassay revealed the presence of humoral immunity inhibition under malnutrition. During protein deficiency there were no circulating autoantibodies against mesenchymal tissue antigens which were found in the serum of the animals fed ad libitum. It is assumed that immune deficiency in malnutrition is also accompanied by inhibition of the so-called enhancement phenomenon in the course of aflatoxin blastomogenesis. It is likely that the immunological mechanisms cited have an effect on the histogenesis as well as on the development of aflatoxin tumors.

[Toxic and metabolic liver injury (author's transl)]. / Toxische Leberschäden.

Water soluble exogenous compounds are commonly excreted by the kidneys, but most of the exogenous substances are lipid soluble and have therefore first to be metabolized in the liver to water soluble compounds. Depending upon the nature of the chemical compound, the metabolism in the liver leads either to detoxification or toxification. Alcohol belongs to the most important substances which may cause severe liver injury. Alterations of the liver due to hydrocarbons as well as carcinogens, mycotoxins and thorium dioxide are relatively rare. Compounds such as analgesic and antiarrhythmic drugs, antibiotics, oral antidiabetic agents, antihypertensive and antirheumatic agents, chemotherapeutic drugs, hormones, laxatives, psychotropic drugs, thyreostatic and antineoplastic agents may also cause liver injury. For establishing the diagnosis, a detailed past history is required especially with respect to alcohol and drug consumption as well as regarding occupational exposure towards toxic compounds. Although the determination of liver enzyme activities in the serum may give some indication for liver cell injury, the histological examination of the liver by needle biopsy is required for the diagnosis. The therapy consists of the exclusion of the toxic compound and, if possible, of an increased elimination of the ingested toxins.