Compensatory lung growth after partial pneumonectomy enhances lung tumorigenesis induced by 3-methylcholanthrene

In small mammals, partial pneumonectomy (PNX) elicits rapid hyperplastic co mpensatory growth of the remaining lung parenchyma to restore normal lung m ass, structure, and function. In BALE mice subjected to PNX, compensatory l ung growth is complete within 10 days. Because cellular hyperplasia contrib utes to the mechanism of tumor promotion by butylated hydroxytoluene (BHT), we hypothesized that hyperplastic compensatory lung growth would promote t umor formation in carcinogen-treated animals in a manner similar to that ob served after BHT. In mice subjected to PNX, within 1 week of treatment with the carcinogen 3-methylcholanthrene (MCA; 10 mu g/g body weight), lung tum or multiplicity was 3-7-fold higher in animals subjected to PNX than in mic e subjected to a sham operation, The increase in tumor multiplicity occurre d when PNX was performed 1, 3, and 6 days before or 1 day after MCA treatme nt. In the absence of PNX, Lung tumor multiplicity in MCA-treated mice give n one injection of BHT (200 mg/kg body weight) increased significantly (P < 0.01) as compared to that in mice given MCA atone, Tumor multiplicity cont inued to increase linearly (R-2 = 0.99) With each subsequent BHT injection. Lung tumor multiplicity and tumor size in mice given one or two injections of BHT were comparable to those in animals subjected to PNX, These data de monstrate that post-PNX compensatory lung growth stimulates tumorigenesis i n MCA-treated mice and provides a novel model for investigating tumor forma tion.