Effect of N-ethyl-N-butyl-nitrosamine on the esophageal mucosa of the rat. Histometric investigation of early tumor stages.

80 male Wistar rats received an oral ad libitum application of N-ethyl-N-butyl-nitrosamine in a concentration of 0.18 g per litre of drinking water. The changes induced in the esophageal mucosa and determined at three intervals (up to 48 days, up to 91 days, and up to 112 days after commencement of carcinogen exposure) were compared by microscopy with the results from a control group of 10 male Wistar rats of the same age. Several histomorphometric parameters were investigated with the aid of a Leitz ocular micrometer. The earliest localized changes found were an increase in the thickness of the epithelium and the horny layer, and an elongation of the papillary bodies and a widening of the parabasal cellular layer. Later--with a substantial increase in the rate of mitosis in all layers of the epithelium, there was a significant thickening of the non-papillomatous and papillomatous epithelium, an enlargement of the nuclei, especially in the middle and upper layers of the epithelium and a thickening of the horny layer, parts of the latter being parakeratotic. The papillomatous changes corresponded in some cases to moderate epithelial dysplasias. As expected, no fully-developed invasive carcinomas occurred in the early period investigated. The histometric data permit the conclusion to be drawn that the lesions described are demonstrable not only at the exophytic-papillomatous epithelium but also in multifocally localized form at the flat, non-papillomatous mucosa, and that they can definitely be regarded as the expression of an incipient field cancerification.