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The Incidence of Cancer in Quantitatively Transplanted Mammary Glands and Its Relation to Age and Milk Agent of the Donor and Host Mice¹

Department of Anatomy, Yale University School of Medicine, New Haven, Connecticut, and Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada

Two hundred fifty-four mammary segments, each 0.6 mm long with little surrounding adipose stromal tissues, obtained from virgin female donor mice of the CBA or C57BL strains, were transplanted into the 4th mammary gland-free fat pads and the pararenal fat pads of F₁ hybrid (CBA x C57BL) hosts. Mammary grafts obtained from milk-agent-free C57BL donors were placed in agent-positive hosts, and those derived from agent-positive CBA donors were placed in agent-free host mice. Mammary grafts from donors of less than 4 months of age were placed in hosts 9 months old or more, and grafts from 19-month-old or older donors were placed in the hosts that were less than 4 months of age at the time of transplantation.

Mammary carcinomas developed in 34 of the 109 successfully transplanted mammary segments; 10 tumors occurred in 12 grafts in female hosts that reared several litters following transplantation, 4 occurred in 12 grafts in castrated male hosts treated with estrogen and progesterone pellets for 12 to 17.5 months, and 20 occurred in 47 grafts in virgin female hosts bearing functional pituitary isografts. In the former 2 groups, only mammary grafts derived from C57BL donors and transplanted into the agent-positive hosts developed cancers. In the last group, mammary cancer did not appear in the hosts in which the pituitary grafts failed to survive. When pituitary isografts were functional, 20 tumors developed in mammary grafts obtained from either C57BL or CBA donors and placed into either agent-positive or agent-free host mice.

Mammary grafts from normal female C57BL donors could be infected with the milk agent present in the environment in the milk-agent-positive hosts and could develop cancer. Also, excessive hormonal stimulation by pituitary isografts overcame lack of the milk agent in the host environment.

The incidence of tumors, the occurrence of histologically different types of mammary cancers in grafts and in the hosts' glands, and the influence of pituitary isografts were examined and discussed in conjunction with the problems of the milk agent and the age of the animals.

¹ Supported by grants from the Anna Fuller Fund, the American Cancer Society Institutional Grants to Yale University School of Medicine, and the Jane Coffin Childs Memorial Fund for Medical Research; by Grant C-343 from the National Cancer Institute, USPHS; and by a grant from the National Cancer Institute of Canada.

² Present address: Cancer Research Laboratory, University of Western Ontario, London, Ontario, Canada.

Received 10/28/64. Revised 5/21/65.