The specific aim of this proposal is to study possible interrelationships between cell proliferation and enhancement of tumor formation in mouse lung. The hypothesis to be tested is that mouse lung tumor formation can be enhanced without concomitant cell proliferation. In two previous and separated experiments we have shown that (a) intraperitoneal injection of the antioxidant butylated hydroxytoluene (BHT) is followed by extensive cell proliferation in mouse lung and this proliferation can be prevented by pretreatment of the mice with SKF 525A*, and (b) if mice are given urethan and then repeated injections of BHT, they develop more tumors than animals given urethan and repeated injections of corn oil. However, enhancement of urethan-induced tumor formation also occurs in animals treated with BHT and SKF 525A. In the proposed experiments, we p]lan to confirm our previous observation that treatment with SKF 525A and BHT enhances tumor formation to the same extent as does BHT alone. At the same time we will verify with autoradiographic techniques that SKF 525A indeed abolished BHT-induced cell proliferation. In additional experiments we will expose urethan-injected mice for 2 weeks to a diet containing 0.75 percent of BHT or give them four weekly intraperitoneal injections of 300 mg./kg. of BHT. Both procedures have been shown to enhance lung tumor formation, and in both experiments qualitative and quantitative information on the extent of overall cell proliferation in lung associated with BHT adminstration will be sought with autoradiography. *SKF 525A*: 2-Diethylaminoethyl-2,2-di-phenylvolerate hydrochloride.
| Witschi, H P (1986) Separation of early diffuse alveolar cell proliferation from enhanced tumor development in mouse lung. Cancer Res 46:2675-9 |
| Witschi, H P; Morse, C C (1985) Cell kinetics in mouse lung following administration of carcinogens and butylated hydroxytoluene. Toxicol Appl Pharmacol 78:464-72 |
