A comparative dose-related response of several key pro- and antiinflammatory mediators in the lungs of rats, mice, and hamsters after subchronic inhalation of carbon black.
OBJECTIVE
The objective of this study was to investigate mechanisms underlying species specificity in particle-induced lung inflammation.


METHODS
Rats, mice, and hamsters exposed to air, 1, 7, or 50 mg/m3 of carbon black for 13 weeks were killed at 1 day, 3 months, and 11 months after exposure. Bronchoalveolar lavage was performed and characterized for cell number, cell type, reactive oxygen and nitrogen species, and cytokine levels. Ex vivo mutational analysis of inflammatory cells was evaluated by coincubating with lung epithelial cells. Lung tissue was evaluated for gene expression of various antiinflammatory mediators.


RESULTS
There was a dose- and time-related effect with all the parameters. Rats demonstrated greater propensity for generating a proinflammatory response, whereas mice and hamsters demonstrated an increased antiinflammatory response.


CONCLUSIONS
These differences in pro- and antiinflammatory responses may contribute to the apparent species differences in inflammation and tumorigenesis.
Carter
Janet M
JM
Procter & Gamble Company, Cincinnati, Ohio 45217, USA. carter.jm.3@pg.com
Corson
Nancy
N
Driscoll
Kevin E
KE
Elder
Alison
A
Finkelstein
Jacob N
JN
Harkema
Jack N
JN
Gelein
Robert
R
Wade-Mercer
Pam
P
Nguyen
Kim
K
Oberdorster
Gunter
G
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000235:genetics / Q000378:metabolism; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D019570:Inhalation Exposure; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D053260:Soot / Q000009:adverse effects*
D016207:Cytokines; D012333:RNA, Messenger; D053260:Soot; D010088:Oxidoreductases; D007041:Hypoxanthine Phosphoribosyltransferase; D005721:Glutamate-Cysteine Ligase