Influence of the Mammary-Tumor Agent on the Genesis of Mammary Cancer in Agent-Free Mice After Male Transmission2

Abstract

Spontaneous mammary cancer will develop in a considerable proportion of the breeding F₁ hybrids produced by mating strain C (BALB/c) females with strain C3H/An males, as determined by Andervont and Dunn and confirmed in this laboratory. The agent could not be demonstrated by bioassay of the tumors from old hybrids unless the mothers became infected and transferred the agent. The data to be considered are concerned with the influence of the mammary-tumor agent (MTA), transferred by males of various sublines of strain C3H, upon the etiology of tumors in F₁ offspring. Hybrids sired by males of strain C3H/AnBi and born in early litters to uninfected strain C mothers had a cancer incidence above 30 percent, while those with strain Z (C3H) fathers and born in later litters to uninfected mothers had an incidence of about 5 percent. The incidences were reversed when strain Z (C3H) males sired early litters and C3H/AnBi males the later ones. Fourteen tumors from hybrids averaging 589 days of age were tested by biological assay, including 1 tumor that appeared at 328 days. Three percent of the test animals had mammary cancer. After the strain C mothers became infected with the MTA, over 90 percent of their F₁ progeny developed mammary tumors at average ages less than 300 days, regardless of the subline of the male parent. At least 20 tumors from infected C mothers and their F₁ progeny were assayed in nearly 1,000 mice, of which 75 percent developed cancer. The tumor-inducing activity of these tumor extracts was higher at dilutions of 10⁻⁴ and 10⁻⁵ than at dilutions of 5 × 10⁻² and 10⁻². There was no indication that the activity of the agent increased with the birth of successive litters. Various theories are discussed which deal with hormone-induced tumors in agent-free animals and the possible origin of the MTA; a suggestion is made of the role of the MTA in the genesis of mammary cancer in mice.