Science Inventory



Kodavanti, U P., M. Schladweiler, A. D. Ledbetter, P. S. Gilmour, P A. Evansky, D L. Costa, W P. Watkinson, AND K. E. Pinkerton. GENETIC SUSCEPTIBILITY AND EXPERIMENTAL INDUCTION OF PULMONARY DISEASE. Presented at ATS Special Conference on COPD, Wikoloa Beach, Hawaii, January 10-12, 2003.


Genetic Susceptibility and Experimental Induction of Pulmonary Disease. UP Kodavanti, MC Schladweiler, AD Ledbetter, PS Gilmour, P Evansky, KR Smith*, WP Watkinson, DL Costa, KE Pinkerton*. ETD, NHEERL, ORD, US EPA, RTP, NC; *Univ California, Davis, CA, USA.
Conventional laboratory rodents have produced minimal inflammation in response to sulfur dioxide (SO2) or tobacco smoke (TS) exposure, and thus, have not yielded reliable models for the study of COPD pathobiology. We propose that multiple genetic risk factors are essential for rodents to respond similar to humans who develop TS-associated COPD. Thus, we used Spontaneously Hypertensive rats (SH), susceptible to oxidative stress, inflammation, and coagulation (all known risk factors for COPD), in the experimental induction of COPD-like disease. Male Sprague-Dawley rats (SD) were used as controls. SH and SD rats were exposed to 0, 250, or 350 ppm SO2, 6 h/d x 4-7 d; SH rats were exposed to TS, 90 mg/m3, 6h/d x 2-15 d. Inflammation, mucus secretion, and systemic responses were analyzed. SH rats produced a 37-fold increase in neutrophils in response to SO2. TS exposure also resulted in a marked neutrophilia in SH rats. This was unlike a 2-fold increase in SD rats. Increased mucus and goblet cells were noted with both exposures in SH rats. Exposure of SH rats to either caused an increase in gamma-glutamyl transpeptidase, a marker for membrane integrity, but not BALF protein. Pulmonary gene expression pattern indicated increased inflammatory and acute stress response genes. Exposure to TS in SH rats decreased glutathione in BALF, and C-reactive protein in serum. This response was associated with a 215 % increase in plasma fibrinogen and a >50% decrease in Factor VIIa and MDA-D dimer. This model is being further evaluated for its similarities to human disease and genetic factors. (Does not reflect USEPA policy).

Record Details:

Product Published Date: 01/10/2003
Record Last Revised: 06/06/2005
Record ID: 62703