Promotion of Lung Tumors in Mice

Abstract

Several elements of two-stage carcinogenesis apply to the development of lung tumors in Strain A or Swiss-Webster mice. At least three agents which have been identified as promoters in skin, urinary bladder and liver will also enhance tumor formation in lung; phorbol, saccharin and butylated hydroxytoluene (BHT). The antioxidant BHT acts in many respects like a typical promoting agent: it is effective if animals are treated after exposure to an initiating agent, but not if they are treated beforehand. Administration of BHT can be delayed up to 5 months after urethan treatment and still enhance tumor formation. BHT enhances lung tumor formation regardless of its route of administration (IP injection, gavage, or ingestion in the diet). The lowest dose of BHT required to produce an effect has not yet been determined. In at least one mouse strain, BHT also enhances tumor formation in animals initiated with 3-methylcholanthrene or dimethylnitrosamine. On the other hand, no evidence is available yet to show that BHT would enhance tumor development in animals treated with subcarcinogenic doses of an initiating compound. Nor has it been possible to produce more tumors with BHT in mouse strains which have a low spontaneous tumor incidence and respond poorly to urethan. The question has not been resolved whether BHT accelerates growth of preformed tumors only or whether it induces the formation of more tumors. Nevertheless, the data collected on the effects of BHT on mouse lung tumor development have broadened the concept of two-stage carcinogenesis and complement the evidence for initiation- promotion available for other epithelial tissues such as liver, colon, stomach, trachea, urinary bladder and mammary gland.