Induced Epithelial Hyperplasia in Organ Cultures of Mouse Mammary Tissues. Effects of the Milk Agent2

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Abstract
Mammary fragments, from agent-free C57BL mice in their first pregnancy, explanted in organ cultures in direct contact with agent-positive RIII milk and stimulated with hormones, presented large areas of invasive epithelial proliferation. A comparable growth response was obtained after the milk was heated at 70° C for 1 hour. Milks from agent-free C57BL and Ax mouse strains also induced a similar type of invasive hyperplasia in the fresh state or after exposure to heat. Purified viral B particles contained in fractions isolated from RIII milk by ultracentrifugal and electrophoretic methods did not induce invasive hyperplasia but stimulated growth and differentiation. It is concluded that the mammary tumor agent is not responsible for the induced invasive epithelial hyperplasia observed in the cultures. However, it might initiate the formation of the highly organized alveolar nodules that usually arise in the mammary glands of high-cancer strains after an incubation period of 4 to 6 months. Heat-labile, inhibiting factors were detected in agent-free C57BL milk. They were also found in fresh milks of agent-positive RIII and A mice where their toxicity seemed greatly diminished. A possible relationship between the presence of such inhibitors and the relative infective potency of the milk agent in different strains of mice is suggested.