Modulating effects of hormones on carcinogenesis.

There is no doubt that hormones have a role in the development of many, perhaps most, cancers. This is because they are vital in maintaining homeostasis in multicellular organisms in which cancer appears. The stage or stages at which hormones are important in the process are not known well, but experiments in animals indicate that hormonal intervention at initiation, promotion, or progression can be important, assuming that such neat division pertains to cancer development in humans (Schmähl, 1985). Hormones may affect initiation through control of the levels of activating and detoxifying enzymes in the liver and other organs, which affect the pharmacokinetics of carcinogens to which the animal is exposed. Hormones control the levels of structural or functional components of some organs, for example, the alpha-2 micro-globulin in the kidney of male rats, which affect the disposition of foreign chemicals. Hormones have enormous influence on growth and development of animals and must play a part in the well-known heightened susceptibility of young animals (including humans) to the effects of exposure to carcinogens. Animals exposed in utero to transplacental carcinogens, or those exposed to single doses as newborns or infants, frequently develop tumors that appear in animals treated as adults not at all or after exposure to much higher doses. Examples are nervous system tumors in rodents exposed transplacentally (Ivankovic, 1979) and liver tumors in rodents treated as infants (Vesselinovitch et al., 1979). It is probable that effects of hormones on cell proliferation are an important part of these effects. From the studies of hormonal effects on carcinogenesis in animals we can conclude that alterations in the function of hormones through inheritance, or through diet, habits, accidents, disease states, or sexual maturity could affect susceptibility of an individual to carcinogens, thereby increasing or decreasing the probability of developing cancer. Compounds with antithyroid properties (e.g., thiouracil or ethylene thiourea, a contaminant and by-product of many thiocarbamates widely used in agriculture and industry) or substances affecting adrenal or pituitary secretions might be implicated as modulators of tumor development, following the leads suggested by experiments in animals described above. Castration, aging, or hypersecretion of sex hormones would also modulate the effects of carcinogens, as they do in experimental animals. There have been few studies of the effects of other hormones such as insulin, gastrin, prolactin, and so forth (Griffin et al., 1955), although these vital hormones vary in distribution even within an individual at different times. An early study (Sugiura and Benedict, 1933) failed to show an effect of treatment with a variety of hormones on the growth of several transplanted tumors. One elusive mystery is why estrogens and diethylstilbestrol induce kidney tumors in Syrian hamsters but not mammary tumors, whereas in rats they give rise to mammary tumors but not to kidney tumors. Obviously we need to know much more about biology in order to better understand the intricacies of neoplastic transformation and development of cancer.