Susceptibility of various strains of mice to urethan-induced lung tumors and depressed natural killer cell activity.
Inbred A/J, CBA/J, and C57BL/6 mice at age 7-8 weeks were inoculated with 1 mg urethan/g body weight. Three months later, 13.2, 1.8, and 0.1 tumors per lung were found in these mice, respectively. Cytotoxicity by spleen cells of normal and urethan-treated mice was analyzed in a 4-hour 51Cr release assay against YAC-1 cells. During the first 2 weeks after treatment, urethan strongly suppressed the cytotoxicity by spleen cells of A/J mice but had relatively little effect on the reactivity of spleen cells of CBA/J mice. Natural killer (NK) activity was not suppressed in urethan-treated C57BL/6 mice. The effect of urethan on natural in vivo antitumor resistance in the lungs was studied by measurement of elimination from the lungs of [125I]-deoxyuridine-labeled YAC-1 cells. Urethan caused profound and sustained suppression of in vivo NK reactivity in the lungs of A/J mice, had only a transient effect on CBA/J mice, and had no detectable effect on C57BL/6 mice. The differences in the effects of urethan on the natural antitumor resistance in the three strains of mice could not be attributed to a generally greater susceptibility of A/J mice to inhibition of NK activity, since cyclophosphamide (0.15 mg/g) equally suppressed the clearance from the lungs of the radiolabeled tumor cells in A/J, CBA/J, and C57BL/6 mice. These results indicate a positive correlation between susceptibility of A/J, CBA/J, and C57BL/6 mice to urethan-induced lung carcinogenesis and inhibition of in vitro and in vivo natural cell-mediated cytotoxicities and support the hypothesis that NK cells play a role in resistance to urethan-induced lung carcinogenesis.
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A / Q000502:physiology*; D008810:Mice, Inbred C57BL / Q000502:physiology*; D008808:Mice, Inbred CBA / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D014520:Urethane / Q000494:pharmacology*
D014520:Urethane