PREVIOUS observations (Foulds, 1947(Foulds, , 1949b showed that the growth of some transplanted mammary tumours in hybrid mice depended on a hormonal stimulus which operated in normal female mice but not in normal males; artificially-administered oestrogen supplied the necessary stimulus for growth in males. Some of the tumours were independent of the hormonal stimulus at the first transplantation; others lost their dependence after several transfers.Dependence on hormones seemed to characterize one stage in the life-history of mammary tumours in hybrid mice. The present paper deals with spontaneous mammary tumours growing in their original hosts; it records cycles of growth and regression of tumours in successive pregnancies, and a progression of the tumours towards independence of hormonal stimuli.
MATERIAL AND METHODSThe investigation comprised repeated measurements of tumours in 275 mice which carried, before death, a total of 655 mammary growths. The majority of the mice were BR hybrids, mostly of the F3 and F4 generations, and made up of 71 mice of strain BR4 (pink label), 90 of strain BR4 (blue label), and 69 of strain BR6. The remaining mice were 28 RB F1 hybrids and 17 BA F1 hybrids. A preceding paper (Foulds, 1949a) describes the source of these hybrids and the incidence of tumours in them.The mice were subjected to forced breeding and most of them had pregnancies in rapid succession throughout the period of observation, even when bearing multiple large tumours. Some intermissions of breeding were attributable to temporary absence of males or to infertility of the males.The mice were inspected twice weekly. Tumours were recognized usually when about 0 5 cm. in diameter, and weekly thereafter two main diameters were measured with calipers. Growth charts were made by plotting the sum of the two diameters against time. Post-mortem measurements usually agreed satisfactorily with those made during life; measurements on regressing tumours were the most difficult and subject to the largest errors. Frequent, often daily, measurements were made on selected mice.Litters were recorded each morning except on Sundays and public holidays. The time of parturition as shown on the charts was usually later than the actual time by unknown periods of up to 24 hours on weekdays and 48 hours at weekends. A more accurate timing was not attempted systematically, but was sometimes achieved, by chance, when mice were examined during parturition.
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.
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