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A series of range-finding studies was conducted in a limited number of male F344 rats on the relation between cell proliferation and styrene oxide (SO) given as gavage doses in corn oil ranging from 550 to 1500 mg SO/kg. In each study, rats were injected with [3H]thymidine (0.50 mCi/g, ip) at intervals from 1 to 48 hr after dosing with SO. One hour later, stomachs were removed and fixed in formalin. Autoradiograms were prepared and labeling index (LI) was determined as the percentage of epithelial cells with 3H-labeled nuclei. Mean LI increased with a peak at approximately 15 hr after one or nine doses of SO. The increases were multifocal and not restricted to the area near the limiting ridge. The magnitude of the response in LI at 24 hr after dosing tended to decrease with progressive multiple doses (3/week). Dose-related morphologic lesions from SO (particularly submucosal) were multifocal and variable across the forestomach; they appeared unrelated to LI in a given area. In a final study, groups of 10 rats were given a single dose of 0, 20, 50, 125, 250, 500, or 800 mg/kg and LI was determined 15 hr later. Mean LI was dose-related with increases up to 250 mg/kg. A maximum response had apparently been reached and higher doses did not cause any further increase in LI. The degree of involvement of cell proliferation in the tumorigenicity of SO remains uncertain; additional studies are suggested to help in the understanding of such a possible relation.

Cell Proliferation in Rat Forestomach Following Oral Administration of Styrene Oxide