부산대학교 도서관

Humans are continuously exposed to radiation and chemicals. Consequently, combined effect on carcinogenesis, i.e., modification of radiation-induced carcinogenesis by post-treatments with chemicals is utmost important in animal experiments.First, we found mice exposed to urethane at early gestational stage (8th day) was sensitive to post-treatment with urethane via mother milk (Cancer Res 1973). More intensive effects were observed in the mice exposed to X-rays (0.36 Gy) at early gestational stage, though in utero radiation exposure itself rarely induced tumors (Environ Mutagen 1984). This suggests that radiation-induced persistent hypersensitivity in the fetus to post-natal urethane treatment for tumor induction remains over the several ten cell-division.In the mouse fetuses exposed to urethane and X-rays at middle gestational stages, atroply of male and female gonads was observed (Br J Cancer 1976), anticipating the recent finding by endocrine disruptors. In addition, radiation and chemical exposure of male and female germ cells resulted in the higher incidence of tumors and congenital malformations in the offspring (Cancer Res 1975, Nature 1982). Furthermore, F1 offspring of mice exposed to radiation were more sensitive to postnatal urethane or TPA treatments, developing a cluster of tumor nodules in the lung (and also skin tumors and leukemia). Transgenerationally transmitted tumor susceptibility is manifested by postnatal environmental agents, leading the recent studies on genomic instability (Mutat Res 1983, 2003, Nature 1990).