Cell Proliferation in Rat Forestomach Following Oral Administration of Styrene Oxide

A series of range-finding studies was conducted in a limitednumber of male F344 rats on the relation between cell proliferationand styrene oxide (SO) given as gavage doses in corn oil rangingfrom 550 to 1500 mg SO/kg. In each study, rats were injectedwith [³H](0.50 mCi/g, ip) at intervals from 1 to 48 hr afterdosing with SO. One hour later, stomachs were removed and fixedin formalin. Autoradiograins were prepared and labeling index(LI) was determined as the percentage of epithelial cells with³H-labeled nuclei. Mean LI increased with a peak at {small tilde}15 hr after one or nine doses of SO. The increases were multifocaland not restricted to the area near the limiting ridge. Themagnitude of the response in LI at 24 hr after dosing tendedto decrease with progressive multiple doses (3/week). Dose-relatedmorphologic lesions from SO (particularly submucosal) were multifocaland variable across the forestomach; they appeared unrelatedto LI in a given area. In a final study, groups of 10 rats weregiven a single dose of 0, 20, 50, 125, 250, 500, or 800 mg/kgand LI was determined 15 hr later. Mean LI was dose-relatedwith increases up to 250 mg/kg. A maximum response had apparentlybeen reached and higher doses did not cause any further increasein LI. The degree of involvement of cell proliferation in thetumorigenicity of SO remains uncertain; additional studies aresuggested to help in the understanding of such a possible relation.