Adenoma Development in Mouse Lung Following Treatment with Possible Promoting Agents

Abstract

We have examined under what conditions it might be feasible to enhance the sensitivity of the mouse lung adenoma bioas-say. In mice given one single dose of urethan, the number of tumors formed can be increased 2-4 fold by repeated treatments with butylated hydroxytoluene (BHT). The minimum number of injections required to increase the number of tumors which develop is 4 and treatment may begin as late as 4 months after urethan and still be effective. BHT has no effect on tumor development in strains of mice resistant to adenoma formation or in susceptible mice treated with other carcinogens. Although it was initially thought that BHT enhances adenoma formation by stimulating type II cell proliferation in lung, new data suggest that massive cell proliferation is not necessarily a prerequisite for enhancement of tumor formation. A dose of BHT too small to produce noticeable type II cell division (50 mg/kg) enhances tumor development, whereas repeated treatment with oxygen, although stimulating cell division in lung, is without effect on tumor development. In addition, treatment of mice with BHT and SKF 525A, which prevents BHT-induced lung damage, enhances tumor formation as efficiently as does BHT alone.