Contribution of Japanese investigators to studies on chemical transformation in vitro.

Japanese investigators have made substantial and continuous contributions to studies on in vitro transformation by chemical carcinogens. The first successful transformation was achieved independently by KAKUNAGA and KUROKI in 1966 in hamster embryo cells with 4-nitroquinoline-1-oxide and its derivatives. 4-Nitroquinoline-1-oxide has been used since then in studies on transformation in many cells including rat liver parenchymal cells, hamster chondrocytes, human diploid fibroblasts, and BALB 3T3 cells. In this review, the contribution of Japanese investigators is reviewed in historical perspective and the cellular and molecular mechanisms of carcinogenesis are discussed on the basis of their results.