Format

Send to

Choose Destination
Regul Toxicol Pharmacol. 2005 Jun;42(1):24-36. Epub 2005 Feb 25.

Effects of styrene and its metabolites on different lung compartments of the mouse--cell proliferation and histomorphology.

Author information

1
BASF Aktiengesellschaft, Experimental Toxicology and Ecology, Z 470, 67056 Ludwigshafen, Germany.

Abstract

Styrene is not carcinogenic in rats but has caused pneumotoxicity and increased lung tumors after inhalation in mice. This study investigated whether styrene-7,8-oxide, ring-oxidized, and side-chain hydroxylated styrene metabolites induce cell proliferation, apoptosis, pathological changes, and glutathione depletion in mice lungs. Intraperitoneal treatment with phenylacetaldehyde and phenylacetic acid (3 x 100 mg/kg b.w./day) increased the levels of apoptosis and cell proliferation in the alveoli without producing any effects in the terminal bronchioli, the target site of tumor formation in mice. Only styrene-oxide (SO) at 3 x 100 mg/kg b.w./day and 4-vinyl-phenol (4-VP) at 3 x 35 and 3 x 20 mg/kg b.w./day, respectively, caused up to 19-fold increases in cell proliferation in the large/medium bronchi and terminal bronchioles; marginal increases in alveolar cell proliferation were noted with SO (1.6-fold) but not with 4-VP. These compounds also caused glutathione depletion in the bronchiolar epithelium and histomorphological changes of the bronchiolar epithelium in large and medium bronchi and terminal bronchioles. Changes were characterized by flattened cells and a loss of the typical bulging of the "dome-shaped" Clara cells, suggesting that Clara cells were primary target cells. The specific reactions of mouse lung to SO and 4-VP could serve as a verifiable hypothesis for the different response of rats and mice with regard to tumor formation.

PMID:
15896440
DOI:
10.1016/j.yrtph.2005.01.002
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center