In Chapter 3 the carcinogenic effects of a variety of hormones within the organism were pre- sented. In Chapter 7 it was noted that in general the carcinogenic action of such endogenous
hormones is their effectiveness as promoting agents. Thus, it would be expected that hormones play a significant role as endogenous modifiers within a multicellular organism.
As noted in Chapter 3, particularly Figures 3.19 and 3.20 as well as Table 3.7, dramatic changes in circulating levels of specific hormones maintained for long periods of time can result in the development of neoplasms, especially in endocrine tissues. In a similar manner, alteration of internal levels of several different hormones can affect the development of neoplasia induced by chemicals and viruses. One of the earlier studies on the effects of alterations in the endocrine status of rats on their susceptibility to chemical hepatocarcinogens was carried out by Bielschowsky (1961). Dramatic inhibition of the development of hepatic neoplasms by thy- roidectomy and adrenalectomy was noted. Administration of growth hormone or cortisone to thyroidectomized animals reversed this inhibition to a very great degree (Figure 8.1). Since these original studies, a number of similar investigations have been carried out. Most of these studies involve carcinogenesis of the liver or mammary gland (Table 8.3). In rat liver, the effects de- scribed by Bielschowsky have been extended by use of a number of different chemical carcino- gens. The predominant effect noted has been an inhibition of carcinogenesis—with the exception of ovariectomy in both the mouse and the rat, which has been reported to enhance carcinogenesis by 2-AAF and urethane respectively (Table 8.3). Hypophysectomy inhibited or eliminated carcinogenesis in rat liver and mammary gland by several different chemical carcino- gens with a notable exception of dimethylnitrosamine (Yamamoto and Weisburger, 1977). Or- chiectomy inhibits carcinogenesis in rat and mouse liver by several different chemical carcinogens, as it did also in one study in rat kidney (Takizawa and Hirose, 1978). Ovariectomy inhibits carcinogenesis in rat mammary glands by both ionizing radiation and DMBA (Table
Figure 8.1 The effect of the endocrine status of male rats given 2-acetylaminofluorene on the induction of liver neoplasms. THYREX, thyroidectomized; ADREX, adrenalectomized; GH, growth hormone; CORT, cortisone. (After Bielschowsky, 1961.)
8.3). In both rats and mice, ovariectomy appeared to enhance chemical carcinogenesis in liver and in mouse kidney when a partial hepatectomy was performed simultaneously (Vesselinovitch et al., 1973). Interestingly, sialoadenectomy (removal of the submandibular salivary gland) in- hibited spontaneous mouse mammary carcinogenesis (Kurachi et al., 1985). In addition, the number of colonic tumors induced by azoxymethane in rats was increased by surgical orchiec- tomy, but most efficiently by chemical orchiectomy plus the antiandrogen cyproterone acetate (Izbicki et al., 1990).