Mammary-tumour incidence in Sprague-Dawley rats treated with 7,12-dimethylbenz(a)anthracene: Effect of pregnancy and lack of effect of unilateral lactation

Abstract

Summary.-Mammary teat removal (thelectomy) was performed unilaterally in female Sprague-Dawley rats at 35 days of age. They were given 7,12-dimethylbenz-(a)anthracene (DMBA) when aged either 55 days or 79 days. One third were unmated; one third were mated one week and one third mated more than 3 weeks after DMBA administration. Animals were killed when tumour-positive or after one year, when mammary lesions had developed in 99 o of rats. The mean latent period for adenocarcinomas was 18-9 + 2-0 weeks. Benign mammary tumours, mainly secretory adenomas, developed significantly later (39-2 + 17 weeks). The rapid unilateral involution of the thelectomized glands at parturition had no effect on the localization of either adenocarcinomas or benign mammary tumours. Pregnancy and delayed DMBA administration markedly reduced the incidence of adenocarcinomas; lactation had no significant effect.In a separate experiment, precocious puberty induced with pregnant-mare-serum gonadotrophin in 30-day-old female Sprague-Dawley rats enabled their first pregnancy and lactation to be completed by 80 days of age. Parity before carcinogen administration significantly delayed the development of adenocarcinomas.

Protective effect of chorionic gonadotropin on DMBA-induced mammary carcinogenesis

“…The comparison of the effect of hCG treatment with that of pregnancy is straightforward with results reported by Grubbs et al (1983aGrubbs et al ( , 1986 and Moore et al (1981), who found a protective effect when pregnancy was initiated soon after carcinogen administration. Dao et al (1960) also reported complete inhibition of tumorigenesis when pregnancy was initiated simultaneously with carcinogen administration, and reduced overall tumour incidence when pregnancy was initiated at a later date, although these authors report decreased latency period and greater short term tumour incidence.…”

“…mammary gland from neoplastic transformation (Dao et al, 1960;Russo et al, 1980Russo et al, , 1987a, whereas pregnancy initiated after carcinogen administration has been reported to shorten the latency period, to accelerate the growth of mammary cancer and to increase the number of active centres (Huggins et al, 1962). Dao et al (1960) also reported shortened latency period in tumour development during pregnancy and increased short term tumour incidence, but decreased overall tumorigenic response, whereas Moore et al (1981) and Grubbs et al (1986) found pregnancy to be protective. It has been shown that the protective effect of pregnancy prior to carcinogen administration is due to induction of differentiation of the mammary gland (Russo et al, 1978(Russo et al, , 1980, however, the exact mechanism of action of each specific hormone prior to or after carcinogen administration is not known.…”

“…An additional factor influencing the susceptibility of the mammary gland to carcinogenesis is the asynchronous development of mammary glands located in different topographic locations. Mammary glands located in the thoracic region develop a greater number of tumours than those located in the abdominal or inguinal regions (Gullino et al, 1975;Moore et al, 1981;Russo et al, 1987a), what is attributed to a delayed differentiation of thoracic mammary glands (Russo et al, 1987a).…”

“…Although it is known that both mammary differentiation and tumorigenesis are modulated by hormones, and that a majority of chemically-induced mammary cancers are hormone dependent, since they can be suppressed by either hormone deprivation, hormone administration, or by pregnancy and lactation (Dao et al, 1960;Grubbs et al, 1983aGrubbs et al, , b, 1986Huggins et al, 1961;McCormick et al, 1973;Moore et al, 1981;Nicholson et al, 1988;Russo & Russo, 1986Welsch, 1985), the definitive role of hormones in tumour progression still remains to be elucidated. mammary gland from neoplastic transformation (Dao et al, 1960;Russo et al, 1980Russo et al, , 1987a, whereas pregnancy initiated after carcinogen administration has been reported to shorten the latency period, to accelerate the growth of mammary cancer and to increase the number of active centres (Huggins et al, 1962).…”

“…The mammary gland of Sprague-Dawley rats exhibits the highest susceptibility to malignant transformation when the carcinogen affects undifferentiated terminal ductal structures or terminal end buds (TEBs) which are present in the immature gland of young virgin animals (Russo et al, 1977(Russo et al, , 1987a. The susceptibility of the mammary gland to neoplastic transformation decreases progressively with ageing and more markedly with differentiation, such as that occurring after full-term pregnancy (Dao et al, 1960;Grubbs et al, 1983aGrubbs et al, , 1986Moore et al, 1981;Russo et al, 1978Russo et al, , 1979Russo et al, , 1980Russo et al, , 1987a. An additional factor influencing the susceptibility of the mammary gland to carcinogenesis is the asynchronous development of mammary glands located in different topographic locations.…”