Comparison of inflammatory lung responses in Wistar rats and C57 and DBA mice following acute exposure to cadmium oxide fumes.
Inhalation of cadmium oxide (CdO) is a significant form of human exposure to cadmium (Cd). Furthermore, there is epidemiological and experimental data relating Cd inhalation with lung cancer. Animal studies indicate that rats are more susceptible to Cd-induced lung cancer than mice, but interstrain sensitivity differences to Cd-induced pulmonary inflammation or carcinogenesis have not been addressed in either species. We compared pulmonary inflammatory processes in Wistar Furth (WF) rats with those in C57 and DBA mice exposed to freshly generated CdO fumes in nose-only inhalation chambers. Animals were exposed to 1 mg Cd/m3 for 3 hr and terminated immediately or 1, 3, and 5 days after exposure. Control animals were exposed to air/argon furnace gases. Cd-induced lung injury was assessed by bronchoalveolar lavage fluid (BALF) analyses, histopathology, and immunohistochemical detection of cell proliferation. Inhalation of CdO resulted in pulmonary inflammatory processes that varied widely across species and strains. C57 mice responded with faster and greater influx of neutrophils and proliferation of alveolar macrophages, type II epithelial cells, and bronchiolar epithelial cells compared to DBA mice or WF rats. DBA mice retained a greater percentage of inhaled Cd in the lungs and presented higher levels of BALF protein than C57 mice or rats. In comparison to mice, WF rats responded with a more transient inflammatory response in BALF parameters and higher degree of acute inflammation in lung tissue. The more pronounced proliferation of alveolar and bronchiolar epithelial cells observed in C57 mice might indicate higher susceptibility of this mice strain to Cd-induced lung carcinogenesis compared to DBA mice or WF rats. Furthermore, the present results of fewer inflammatory cells and lower proliferation of epithelial cells in DBA mice in association with our previous observation of higher Cd-induced metallothionein protein in this strain suggest that DBA might be less susceptible to the pulmonary carcinogenic effects of inhaled Cd than C57 mice or WF rats. We conclude that mice might not necessarily be more resistant than rats to the carcinogenic effects of inhaled Cd, since intraspecies susceptibility differences are strongly suggested by the present data. An extrapolation of this conclusion is that genetic variations in the human population may determine individual sensitivity differences to inhaled Cd.
McKenna
I M
IM
Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702, USA. mckennai@bprb.nci.nih.gov
Waalkes
M P
MP
Chen
L C
LC
Gordon
T
T
D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry* / Q000166:cytology; D002104:Cadmium / Q000032:analysis*; D019187:Cadmium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009504:Neutrophils / Q000187:drug effects; D010087:Oxides / Q000008:administration & dosage / Q000633:toxicity*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D019187:Cadmium Compounds; D010087:Oxides; D018809:Proliferating Cell Nuclear Antigen; D002104:Cadmium; C029663:cadmium oxide