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Lung Tumorigenic Response of Strain A Mice Exposed to Hypoxic Cell Sensitizers Alone and in Combination with -Radiation¹

School of Public Health, The University of Texas, Health Science Center at Houston, [T. A. M., J. C. T.], and Department of Experimental Radiotherapy, The University of Texas System Cancer Center, M. D. Anderson Hospital and Tumor Institute [D. J. G.], Houston, Texas 77030

The influence of metronidazole, misonidazole, and desmethylmisonidazole on the induction of lung adenomas in the strain A mouse was examined. Two dose levels of the hypoxic cell sensitizers, 0.2 and 0.6 mg/g, were used either alone or in combination with 900 rads of -radiation in a fractionated dose schedule of twice a week for 3 weeks. In the groups of mice which received hypoxic cell sensitizers only, the prevalence and the mean number of lung tumors per mouse were somewhat increased (p < 0.10) in the group receiving the higher dose (0.6 mg/g) of misonidazole but was not significantly different from results for the control animals in the other two sensitizer groups. The combination of hypoxic cell sensitizer and radiation did not show any significant enhancement of lung tumor response when compared with the group which received radiation only. The dose of radiation used in this study significantly enhanced lung tumor formation in mice when compared with that in the control group. Thus, under the experimental exposure conditions used in this investigation, which were somewhat similar to the exposure conditions occurring in clinical treatment, each of the hypoxic cell sensitizers tested failed to sensitize significantly the mice to the carcinogenic effects of -radiation.

¹ This investigation was supported by Research Grant CA 18628 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 4/19/82. Accepted 10/11/82.