CC10 mRNA and protein expression in Clara cells of CD-1 mice following exposure to styrene or its metabolites styrene oxide or 4-vinylphenol

Harvilchuck, J.A.; Zurbrugg, R.J.; Carlson, G.P.

Toxicology Letters 183(1-3): 28-35

2008


ISSN/ISBN: 0378-4274
PMID: 18926891
DOI: 10.1016/j.toxlet.2008.09.010
Accession: 051887311

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Abstract
Styrene, widely used in manufacturing, has both acute and chronic effects in humans. In mice, styrene is both hepato- and pneumo-toxic and causes lung tumors. The primary site for styrene metabolism and its effects in mouse lung is the Clara cell, which secretes Clara cell 10kDa protein (CC10) and surfactant protein A (SPA). Both play important roles in host defenses and inflammation prevention. The mode of action for styrene-induced lung tumor formation has yet to be elicited, yet one possibility relates to oxidative stress and decreased CC10 levels. CC10 mRNA and protein expression were measured in isolated Clara cells 3, 12, and 24h following in vivo administration of styrene (600mg/kg i.p.) or its metabolites [R-, S-, racemic styrene oxide (SO) (300mg/kg i.p.), 4-vinylphenol (100mg/kg i.p.)]. The largest decreases in CC10 mRNA expression were seen with R-SO and racemic SO at 24h. To determine if rebound effects would be seen, CC10 mRNA and protein expression were determined 48, 120, and 240h following styrene and R-SO administration. The CC10 protein level did not reach its lowest point to correlate with mRNA expression until 120h after R-SO administration. Styrene exposure caused a significant decrease in CC10 protein after 24h, rebounding through 240h. SPA protein expression showed little change from control levels, indicating a more specific effect on CC10 in the Clara cell by styrene and its metabolites. These studies demonstrate that acute changes in lung CC10 protein and mRNA expression do occur following in vivo treatment with styrene and its metabolites. These changes may be early indicators for a potential mechanism for lung tumor formation in mice as it relates to oxidative stress and the possibility deserves further study.