Detection of mutagens-carcinogens: carcinogen-induced lesions pinpointed by alkaline phosphatase activity in fixed...

Alkaline phosphatase (AP) activity was not detectable by histochemical staining in the glandular stomachs of normal rats. However, AP activity was present at high levels in the brush borders of the intestine and persisted after fixation of the tissues in Formalin at room temperature. Foci of AP activity were detected in gross Formalin-fixed specimens of glandular stomachs of male and female inbred F344 rats exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and killed over 6 years ago. The incidence of AP-positive foci increased in proportion to the dose of the carcinogen MNNG. Histologically, most of the grossly visible AP-positive foci corresponded to areas of intestinal metaplasia and adenocarcinoma. AP-positive foci localized sites of pathologic significance for microscopic examination and pinpointed gastric sites containing very early tumors that were missed by standard examination.