Mammary Tumours in Hybrid Mice: A Sex-factor in Transplantation

Abstract

For many experiments hybrid mice obtained by crossing two inbred strains are preferable to either of the contributory pure lines. The F1 hybrids, although not homozygous, are uniform in genetic constitution, they manifest " hybrid vigour," and reciprocal crosses permit the study of different maternal factors in conjunction with the same genotype. Mammary tumours develop unexpectedly and erratically in some hybrid and pure line mice supposedly deficient in the maternal milk agent which, according to Bittner (1942) and others, co-operates with oestrogenic stimulation and appropriate genetic constitution to evoke mammary tumours in mice of " high cancer" strains. The mammary tumours described in this paper developed In hybrid mice which were presumed deficient in the milk agent. Several of the tumours were readily transplantable into female but not into male mice of appropriate genetic constitution, and experiments showed that hormones controlled the outcome of transplantation.

A Study of the Development of Mammary Tumours in Hybrid Mice

“…The appearance of mammary tumours in some of the (C57 x RIII)F1 hybrid females following forced breeding could be explained by the transmission of small amounts of the agent by their C57 Black strain mothers after mating to RIII strain males, as originally suggested by Foulds (1949), although none of the C57 females developed breast cancer, and further by activation of the agent in their susceptible hybrid progeny by increased hormonal stimulation. The observation that none of the C57 strain females developed mammary tumours after mating to C57 strain males and forced breeding points against the possibility of C57 Black strain females harbouring a weak or attenuated mammary tumour agent.…”

“…Biological tests for the presence of the agent in some of these tumours as well as a study of the microscopical appearance of breast cancer in these mice are now complete, and a full account of this investigation is now possible. During the intervening years, since the present experiments were started, the problem of the origin of breast tumours in hybrid mice of various derivations has also engaged the attention of several other investigators (Foulds, 1947(Foulds, , 1949 Andervont and Dunn, 1948aDunn, , 1948bDunn, , 1949Dunn, , 1950b Andervont, 1950a; Bittner, 1952a;Muhlbock, 1952 (Dmochowski and Gye, 1943) has with small variations remained approximately the same. It was known that mice of high-cancer strains derived from the fourth or later litters develop a higher incidence of breast cancer than those from the first two litters (Bittner, 1942), and that the appearance of an active agent in mice deprived of it by foster nursing had been recorded in the progeny obtained from the third or later litters (Bittner, 1943).…”

“…Further, an increase in the amount of the tumour agent as a result of securing later litters for obtaining progeny for each successive generation and its C4 cq activation by inbreeding and intensive hormonal stimulation (forced breeding) must also be taken into consideration as a possible cause of the increasing number of tumorous females born in the first litter in each successive generation. Foulds (1947Foulds ( , 1949 reported an incidence of 15 per cent of mammary tumours at an average age of 10 months in forcibly-bred hybrids of similar derivation.…”

“…The difference in the age of the earliest tumour appearance in the descendants of these two types of [ (1)82 (1 hybrid females was less apparent, and in the later generations of the progeny of non-tumorous hybrid females it was even lower than that in the progeny of tumorous (C57 x RIII)F1 hybrids. It may be of interest to point out that Foulds (1949) recorded a very low breast tumour incidence (1 to 3 per cent) at a late age (16 months) in forcibly-bred progeny of a non-tumorous (C57 x RIII)F1 hybrid compared with a high (70 per cent) at 11 months in the progeny of three tumorous (C57 x RIII)F1 hybrid females. The age of the earliest tumour appearance and the average tumour age in the progeny bred in a normal way of one cancer-free (C57 x RIII)F1 hybrid female was distinctly higher than those in the forcibly-bred progeny of both tumorous and tumour-free (C57 x RIII)F1 hybrids.…”

“…It is therefore possible that the results of the comparison of normally with forciblybred progeny of non-cancerous hybrids would have been different as in the case of the comparison of forcibly-bred progeny of non-tumorous with that of tumorous hybrids. It is not known whether the results of Foulds' (1949) comparison of forcibly-bred progeny from tumorous and non-tumorous hybrid females would (1)9…”