Tumorigenesis in B6C3F1 mice exposed to ozone in combination with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and dietary dibutyl phthalate

Abstract

Although ozone exposure has been suspected as a risk factor for the development of lung cancer, data are still inconclusive. Studies in the literature infrequently recognize that the potential toxicity of ozone could be influenced by the combined exposure with other environmental carcinogens. To evaluate the carcinogenic potential of ozone alone or in combination with other toxicants, male and female B6C3F1 mice were exposed through inhalation and diet, to 0.5 ppm of ozone, 1.0 mg/kg of 4- (N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 5000 ppm of dibutyl phthalate (DBP), individually and in combination for I year. No treatment-related death was seen, but significant differences in body and organ weights between control and treated mice were observed during the study. No tumor incidence was found in mice of either gender exposed to ozone alone. Pulmonary neoplasms were found in both, male and female mice exposed to NNK alone and in combination, ozone with NNK only or NNK plus DBP. Oviductal carcinomas were observed in females exposed to DBP alone and together with ozone plus NNK. These results indicate that ozone alone is not a lung carcinogen and in conjunction with NNK and/or DBP have no effect on tumor development in B6C3F1 mice under our experimental conditions. Toxicology and Industrial Health 2009; 25: 189-195.