The Influence of Pseudopregnancy on the Induction of Mammary Tumours by Methylcholanthrene in Mice of the Balb/c Strain

Abstract

MAMMARY carcinomas can be induced in virgin IF female mice by means of chemical carcinogens (Bonser, 1958). But it was shown by Bonser (1954) that oestrogen alone was not a sufficient substitute for the ovaries as the hormonal stimulus in the induction of such tumours by methylcholanthrene. However, by replacement of the ovarian steroid hormones by oestrogen and progesterone, Jull (1954) was able to obtain 9 tumours in 11 ovariectomised mice. He also demonstrated (1953) that virgin females of this strain have a well-developed duct and acinar system, the latter reaching a maximum at about 18 weeks of age but showing much individual variation. This extensive acinar development and the demonstration by van der Lee and Boot (1955) that spontaneous pseudopregnancy is frequent in virgins of some mouse strains when the females are caged in groups, suggested that high levels of progesterone might be operating in the IF female and might account for the high incidence of breast tumours induced by chemical carcinogens. It was therefore decided to test the effect of repeated induced pseudopregnancies on tumour induction by a chemical carcinogen.The strain chosen was the BALB/c, which does not carry the milk factor (Andervont, 1940) and has a low incidence of spontaneous mammary cancer. The only information available regarding the reaction of this strain to chemical carcinogens was that obtained by Squartini (1958) who had failed to induce mammary tumours in 30 virgin mice by means of subcutaneous injection of 1 mg.of 20-methylcholanthrene in 0.2 c.c. of olive oil. There was, therefore, no guide in regard to the dose and duration of the chemical treatment to be adopted. In order to gain an insight into the mode of action of the chemical, it was decided to test three groups of mice: virgins kept five in a cage; virgins deprived of the olfactory lobes and kept singly in order to reduce pseudopregnancy to a minimum (van der Lee and Boot, 1956); and virgins kept with vasectomised males in order to induce pseudopregnancy.

The Influence of Pseudopregnancy on Breast Tumour Induction in C57B1 Mice by Various Chemical Carcinogens

“…In this connection, it is of interest that the unexpected appearance of a breast tumour in the last survivor of the pseudopregnant group of C57B1 treated with DAIBA was associated with a large ovarian tumour, which may have been the source of the hormonal stimulation required for its development. The C3Hb virgin female mice used by Biancifiori et al (1961) might have been expected, on Jull's (1956) hypothesis, to be rather insensitive to breast tumour iniduction bv DMBA and MC, since they have a rather low incidence of spontaneous pseudopregnancy. They were, however, found to be fairly sensitive to these carcinogens, both of which produced a good yield of granulosa-celled tumours of the ovaries, at about the same time as the development of the mammarv tumours.…”

“…Such waning may be due to the age of the mice, or to the effect of the carcinogen treatment on their ovaries. Of the 4 carcinogens used, DMBA is known to have by far the greatest effect upon mouse ovaries (Mody 1960Biancifiori et al 1961. It rapidly causes the destruction of oocytes and this is followed by the disappearance of the corpora lutea (Marchant, 1959).…”

“…V'irgin female mice of the BALB/c, DBA, L(P) and C57B1 strains are all resistant to breast tumour induction by MC, but are susceptible if maintained in a state of pseudopregniancy by caging them in the presence of vasectomised males, (Biancifiori, Bonser and Caschera, 1959;Ranadive, Hakim and Kharkar, 1960;Marchant, 1961a). The susceptibility of breast tissue of virgin mice of strains such as the IF to tumour induction by MC may be attributed to the high incidence of sponitaneous pseudopregnancy occurring when these animals are caged in groups (Muhlbock and Boot, 1960).…”

“…Thus, like MC, the progesterone-mimetic DMBA is capable of inducing breast tumours when high levels of progesterone are operating. When these 4 carcinogens were tested on agent-free C3Hb virgins, which have a low incidence of spontaneous pseudopregnancy, the greatest incidence of tumours was obtained after MC; DMBA produced fewer tumours but they occurred much earlier than with MC; DBA was only slightly effective and BP ineffective in inducing breast tumours, (Biancifiori, Bonser and Caschera, 1961).…”

The Effects of Hormonal Environment on Mammary Carcinogenesis in C3Hb Mice by 1,2:5,6-Dibenzanthracene

“…Jull (1958) reported an incidence of 43 per cent in virgin IF mice given 4 fortnightly skin applications of an 0-25 per cent solution of this compound in arachis oil, and Biancifiori et al (1961) found 4 breast tumours in 15 virgin female C3Hb mice treated 8 times at weekly intervals by skin painting, but none arose in 15 mice treated for 8 weeks with the carcinogen by stomach tube.…”