Ozone activates transforming genes in vitro and acts as a synergistic co-carcinogen with γ-rays only if delivered after radiation

Abstract

An earlier study indicated that ozone (O₃), a major pollutant in our atmosphere, acts as a carcinogen as well as a synergistic co-carcinogen with radiation in cultured hamster embryo cells and in mouse C3H10T1/2 cells. In this investigation we further characterize the oncogenic action of ozone, alone or in combination with radiation, on C3H10T1/2 cells with particular emphasis on transformation produced by different temporal patterns of dose delivery of these two agents and low dose effects. We report that ozone-induced transformation involves the activation of dominant transforming genes, thereby indicating that DNA is a target in ozone induced carcinogenesis. We also report that ozone (5 p.p.m. for 5 min) acts as a synergistk co-carcinogen only if delivered after radiation (4 Gy or γ-rays); when cells are exposed to ozone prior to radiation no enhanced rates of transformation are observed. Our findings also show that ozone at a low dose of 1 p.p.m. (for 5 min) does not act as a carcinogen but does interact as a co-carcinogen with ionizing radiation. The data indicate that the dose and sequence in which ozone and radiation are delivered have important implications for the putative carcinogenic effects of these two agents, a factor that heretofore has not been recognized.