Unscheduled DNA Synthesis in Hamster Tracheal Epithelium Exposed in Vitro to Chemical Carcinogens and Environmental Pollutants

Abstract

The Syrian golden hamster has been used extensively for studies of respiratory carcinogenesis (Saffiotti, 1969; Nettesheim, 1972; Becci et al., 1978). Using organ cultures of the target tissue (i.e., respiratory epithelium) obtained from the hamster, a middle ground has been established between animal experiments and the use of cell cultures for carcinogenesis research (Saffiotti and Harris, 1979). Metabolic studies on environmental chemical carcinogens have been conducted with tracheas of hamsters (Harris et al., 1973; Kaufman et al., 1974). Some carcinogens can be metabolically activated in the tracheal epithelium, and their interaction with cellular macromolecules can be localized at the molecular level by biochemical techniques or at the cellular level by autoradiography. Studies in cultured human bronchus have shown that the metabolic pathway leading to the major benzo(a)pyrene (B[a]P)-DNA adducts is similar to that found in hamsters (Harris et al., 1978). Sixty-five percent of the B(a)P bound to DNA in human cells was removed after 10 days in culture. Since a variety of mammalian cells, including human, can repair damage to DNA caused by chemical carcinogens, it was speculated that DNA repair was responsible for this observation. Thus, by using hamster tracheas in organ culture maintaining specific metabolic enzymes, we may obtain a system relating to human respiratory carcinogenesis that is useful for screening environmental chemicals and complex mixtures capable of damaging DNA.