Strain-dependent differences in susceptibility to lung cancer in inbred mice exposed to mainstream cigarette smoke

It is becoming increasingly clear that genetic susceptibility is an important host factor determining the effects of exposure to a number of airborne particles and gases. Although numerous studies have identified a genetic component for spontaneous pulmonary tumor development and for chemically induced lung cancer (e.g., urethane) in mice, a systematic examination of murine inter-strain differences in response to cigarette smoke inhalation has not been conducted. We addressed this research gap by examining the strain distribution pattern of lung cancer in nine inbred strains of mice exposed to 258 mg/m(3) mainstream cigarette smoke for 5 months followed by 4 months of rest. Lung tumors were enumerated on fixed lungs visualized at low magnification and on serial step sections examined microscopically. With the low magnification examination, we observed statistically significant increases in the number of lung tumors in cigarette smoke-exposed A/J and the genetically-related A/HeJ mice (p<0.05). While fewer tumors were identified by the microscopic enumeration method, it confirmed that significant increases in lung tumors occurred only in A/J and A/HeJ mice exposed to cigarette smoke (p<0.05). Thus, as predicted by epidemiologic studies and animal experiments using chemically induced lung cancer models, these findings suggest that genetic host factors play a significant role in the pulmonary tumorigenic response of mice to mainstream cigarette smoke.