Genetic Selection For High Acute Inflammatory Response Confers Resistance To Lung Carcinogenesis In The Mouse

Abstract

Mice selected for a high acute inflammatory response (AIRmax) are resistant to chemically induced lung tumorigenesis, whereas the low responders (AIRmin) are susceptible. In urethane-treated mice, anti-inflammatory drugs increased the tumor incidence in AIRmax but not AIRmin mice, and an inverse correlation (P<.001) between the degree of acute inflammatory response (AIR) and lung tumorigenesis was found in an F2 (AIRmax×AIRmin) intercross population. The results provide evidence for the involvement of lung tumor modifier loci in AIR regulation and implicate AIR quantitative trait loci in the inherited predisposition to lung cancer.

Key Words::

• acute inflammation
• genetic selection
• lung chemical carcinogenesis
• mouse

Notes

This work was partially funded by grants from Fundac¸ão de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Pesquisas (CNPq), and Fundac¸ão Butantan.