Energy restriction that inhibits cellular proliferation by torpor can decrease susceptibility to spontaneous and asbestos-induced lung tumors in A/J mice.

Abstract

BACKGROUND: Energy restriction (ER) inhibits various tumors in mice. A/J mice have a very high incidence of lung tumors, that are correlated with elevated levels of pulmonary cell proliferation in this strain. Using A/J mice, we studied the effects of ER on spontaneous and asbestos-induced lung tumors and on labeling indices in the lung as a proximal marker of susceptibility to lung tumors to obtain better understanding of the mechanism of ER in reducing tumorigenesis. EXPERIMENTAL DESIGN: Experiment 1: A/J female mice were instilled intratracheally with asbestos or titanium dioxide or simple saline at 20 weeks of age. At 21 weeks of age, mice of the ER diet group were switched from the control diet (350 kJ/week) to the ER diet (175 kJ/wk) until sacrifice at 105 weeks of age, whereas mice of the control diet group were continued on the control diet. Experiment 2: A/J female mice were begun on ER or control diets at 6 weeks of age. The control and ER mice were kept at 20 to 22 degrees C, whereas mice of another ER group (ER+I) were kept at 30 degrees C until 24 weeks of age. Body temperatures of these mice were monitored by telemetery. RESULTS: The present ER was shown to suppress the development of both asbestos-induced and spontaneous lung tumors. ER mice were confirmed to become torporfic, whereas control and ER+I mice did not. Labeling indices were reduced by ER in the lung as well as in other organs. The reduction of labeling indices was, however, almost recovered by increasing the housing temperature to 30 degrees C. CONCLUSIONS: ER which reduces cellular proliferation in various organs by torpor was shown to inhibit lung tumors. Inhibition of lung tumors by ER is likely to involve a decrease in cell proliferation.