Compensatory lung growth after partial pneumonectomy enhances lung tumorigenesis induced by 3-methylcholanthrene.
In small mammals, partial pneumonectomy (PNX) elicits rapid hyperplastic compensatory growth of the remaining lung parenchyma to restore normal lung mass, structure, and function. In BALB mice subjected to PNX, compensatory lung growth is complete within 10 days. Because cellular hyperplasia contributes to the mechanism of tumor promotion by butylated hydroxytoluene (BHT), we hypothesized that hyperplastic compensatory lung growth would promote tumor formation in carcinogen-treated animals in a manner similar to that observed after BHT. In mice subjected to PNX, within 1 week of treatment with the carcinogen 3-methylcholanthrene (MCA; 10 microg/g body weight), lung tumor multiplicity was 3-7-fold higher in animals subjected to PNX than in mice subjected to a sham operation. The increase in tumor multiplicity occurred when PNX was performed 1, 3, and 6 days before or 1 day after MCA treatment. In the absence of PNX, lung tumor multiplicity in MCA-treated mice given one injection of BHT (200 mg/kg body weight) increased significantly (P < 0.01) as compared to that in mice given MCA alone. Tumor multiplicity continued to increase linearly (R2 = 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 demonstrate that post-PNX compensatory lung growth stimulates tumorigenesis in MCA-treated mice and provides a novel model for investigating tumor formation.
Brown
L M
LM
Department of Cellular and Molecular Physiology, College of Medicine, Pennsylvania State University, Hershey 17033, USA.
Malkinson
A M
AM
Rannels
D E
DE
Rannels
S R
SR
D000818:Animals; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D008168:Lung / Q000254:growth & development*; D008175:Lung Neoplasms / Q000139:chemically induced*; D008297:Male; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D011013:Pneumonectomy
D002084:Butylated Hydroxytoluene; D008748:Methylcholanthrene