Hormones as Endogenous Modifiers of Carcinogenesis

27 May

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).

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