Resistance to serum-induced terminal differentiation in normal human tracheobronchial epithelial cells after in vivo exposure to 7,12-dimethylbenz[a]anthracene.

Normal human tracheobronchial epithelial cells (NHTBECs) from nine donors were used to repopulate de-epithelialized rat tracheas. After transplantation into nude mice and treatment with 7,12-dimethylbenz[a]anthracene (DMBA), the transplants were removed at 3, 4, 5 and 6 months. Epithelial cells from DMBA-treated tracheas were subculturable. Epithelial cells from most untreated tracheas were not subculturable. After treatment with 0.5, 1, 2, 4, 6 and 8% serum, cells exhibited increased subculturability after in vivo treatment with DMBA, did not terminally differentiate and were still proliferating even in medium containing 8% serum. Karyotypes from these cells showed considerable aneuploidy. Although these cells did not survive for more than 10 subcultures (42 weeks), this was considerably longer than the survival of control cells. Because of their longer survival, resistance to serum-induced terminal differentiation and chromosome alterations, they were considered to be phenotypically altered or partially transformed cells produced by in vivo treatment of human cells with a chemical carcinogen.