Chronic nose-only inhalation study in rats, comparing room-aged sidestream cigarette smoke and diesel engine exhaust.
Nose-only exposure of male and female Wistar rats to a surrogate for environmental tobacco smoke, termed room-aged sidestream smoke (RASS), to diesel engine exhaust (DEE), or to filtered, fresh air (sham) was performed 6 hours/day, 7 days/week for 2 years, followed by a 6-month post-exposure period. The particulate concentrations were 3 and 10 mg/m3. Markers of inflammation in bronchoalveolar lavage showed that DEE (but not RASS) produced a dose-related and persistent inflammatory response. Lung weights were increased markedly in the DEE (but not RASS) groups and did not decrease during the 6-month post-exposure period. Bulky lung DNA adducts increased in the RASS groups, but not in the DEE groups. Cell proliferation in the lungs was unaffected by either experimental treatment. Histopathological responses in the RASS groups were minimal and almost completely reversible; lung tumors were similar in number to those seen in the sham-exposed groups. Rats exposed to DEE showed a panoply of dose-related histopathological responses: largely irreversible and in some cases progressive. Malignant and multiple tumors were seen only in the DEE groups; after 30 months, the tumor incidence (predominantly bronchiolo-alveolar adenomas) was 2% in the sham-exposed groups, 5%in the high RASS groups, and 46% in the high DEE groups (sexes combined). Our results suggest that in rats exposed to DEE, but not to RASS, the following series of events occurs: particle deposition in lungs --> lung "overload" --> pulmonary inflammation --> tumorigenesis, without a significant modifying role of cell proliferation or DNA adduct formation.
Stinn
Walter
W
Philip Morris Research Laboratories GmbH, Cologne, Germany.
Teredesai
Ashok
A
Anskeit
Erwin
E
Rustemeier
Klaus
K
Schepers
Georg
G
Schnell
Peter
P
Haussmann
Hans-Juergen
HJ
Carchman
Richard A
RA
Coggins
Christopher R E
CR
Reininghaus
Wolf
W
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000336:Aerosols / Q000737:chemistry; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001984:Bronchial Neoplasms / Q000139:chemically induced / Q000473:pathology; D002244:Carbon / Q000032:analysis; D002263:Carboxyhemoglobin / Q000378:metabolism; D015197:Carcinogenicity Tests / Q000295:instrumentation / Q000379:methods; D004435:Eating / Q000187:drug effects; D005260:Female; D019570:Inhalation Exposure / Q000032:analysis / Q000706:statistics & numerical data; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009538:Nicotine / Q000378:metabolism / Q000652:urine; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology; D012142:Respiratory Tract Neoplasms / Q000139:chemically induced / Q000473:pathology; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000032:analysis*; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
D000336:Aerosols; D000393:Air Pollutants; D014028:Tobacco Smoke Pollution; D001335:Vehicle Emissions; D009538:Nicotine; D002244:Carbon; D002263:Carboxyhemoglobin