Diethylnitrosamine may induce esophageal dysplasia after local intramural administration

To assess the possibility of promoting esophageal squamous cell carcinoma after direct administration of diethylnitrosamine (DEN) into the wall of the esophagus.

Adult male Wistar rats weighing 250-300 g were used in the studies. Via laparotomy, solution of DEN (at the volume of 0.1 ml) was injected directly into the esophageal wall. Animals were divided into 3 groups: CONTROL group--injected with saline, DEN1 group--injected with DEN 100 mg, DEN2 group--injected twice with DEN at the dose of 100 mg with 7 days interval (total dose of 200 mg).

Microscopic evaluation after 180 days revealed signs of esophagitis in 20% and 30% subjects in DEN1 and DEN2 group respectively. In 30% of animals from DEN1 and 50% animals from DEN2 group, low-grade dysplasia was recognized. The difference between DEN2 and control animals was statistically significant with p < 0.03. Neither high-grade dysplasia nor invasive carcinoma were found in both experimental groups. None of the liver specimens showed the evidence of pathology.

These initial results may indicate the possibility of development of premalignant lesions after local administration of carcinogen into esophageal wall. Observed changes were limited exclusively to esophagus which became the "target organ" in this model.