Effects of short-term cigarette smoke exposure on Fischer 344 rats and on selected lung proteins.
A short-term 5-day cigarette smoke exposure study was conducted in Fischer 344 rats to identify smoke-induced lung protein changes. Groups of 10 male and 10 female rats at 5 weeks of age were randomly assigned to one of four exposure groups. Animals received filtered air (control) or 75, 200, or 400 mg total particulate matter (TPM)/m(3) of diluted Kentucky reference 3R4F cigarette smoke. Nose-only exposures were conducted for 3 hours/day for 5 consecutive days. Mean body weights were significantly reduced only in male rats exposed to 400 mg TPM/m(3). Body weight gains were significantly reduced in 200- and 400-mg TPM/m(3)-exposed males and in all smoke-exposed females compared with controls. Alveolar histiocytosis increased slightly in all smoke exposed-females and 200- and 400-mg TPM/m(3)-exposed males. Cyclooxygenase-2 staining increased at 400 mg TPM/m(3). Matrix metalloproteinase-12 staining of alveolar macrophages and bronchiolar epithelia increased in smoke-exposed animals, especially 400-mg TPM/m(3)-exposed females. Protein kinase C-alpha staining increased in macrophages at 200- and 400-mg TPM/m(3) doses. c-Jun NH(2)-terminal kinases staining decreased in smoke-exposed tissues. The identified changed proteins play roles in inflammation, transformation, proliferation, stress activation, and apoptosis.
Carter
Charleata A
CA
A. W. Spears Research Center, Lorillard Tobacco Company, Greensboro, North Carolina 27405, USA. charleatacarter@lortobco.com
Misra
Manoj
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000096:biosynthesis / Q000187:drug effects; D011493:Protein Kinase C / Q000096:biosynthesis / Q000187:drug effects; D011506:Proteins / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology; D013995:Time; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D011506:Proteins; D014028:Tobacco Smoke Pollution; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D053508:Matrix Metalloproteinase 12