Neoplastic transformation of epithelial cells in whole mammary gland in vitro.

Abstract

Biological characteristics of nodule-like alveolar lesions (NLAL) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in organ culture of whole mammary gland (BALB/c female mice) were assessed after transplantation into gland-free mammary fat pads of syngeneic virgin mice. Tissue-fragment explants from NLAL areas of the gland produced abnormal lobuloaveolar (LA) outgrowths in 3 of 10 fat pads. Transplantation of dissociated cells of NLAL-derived LA outgrowths into 36 fat pads showed 100% LA outgrowths and 3 (8%) of these 36 outgrowths produced mammary carcinomas. The explants of dissociated cells from whole mammary glands treated with DMBA in culture produced full or partial LA structures in 2 of 56 outgrowths. The explants of dissociated cells prepared from outgrowths derived from explants as in the preceding statement produced 9 LA outgrowths in 16 instances; mammary tumor incidence in these outgrowths was 3 of 16 (18%). The explants of tissue fragments from LA outgrowths as in the preceding statement produced LA outgrowths in 20 of 20 fat pads; mammary carcinomas appeared in 16 of 20 (80%) of these outgrowths. No NLAL was detectable in control glands treated with dimethyl sulfoxide (solvent for DMBA); explants of the control glands consistently produced ductal outgrowths and no tumor. This accomplishment of chemical carcinogen-induced neoplastic transformation of epithelial cells in vitro provides a model for studying carcinogenesis in an entire isolated organ.