Further studies on the carcinogenic-free interval following exposure in experimental esophageal tumorigenesis

247 C57B1 male mice were killed after Diethylnitrosamine (DEN) treatment at various time intervals ranging from one day to nine months. The number of esophageal tumors was divided by the length of the resected esophagus (i.e. Tumor Index = TI). Animals treated for up to 2 months had a TI of 0.1. Since the histological examination of the esophagi in those animals revealed only normal histology, the conclusion drawn was that the TI of 0.1 was a methodological error in assessing esophageal tumors by transillumination. Three months' treatment with DEN resulted in a 9-fold increased TI and 6 months' treatment in a 69-fold increased TI. Other groups of animals treated with DEN for the same period of time were allowed to survive 7, 9 or 12 months without further treatment. Animals treated with DEN for 1 day but followed without further treatment for 7 months demonstrated a 3.5-fold increased TI. For animals treated with DEN for only 14 days, (TI 0.1) and followed for 7 months with a carcinogenic-free diet, a 7-fold TI was observed. For the group of animals treated for 3 months (TI 0.9) but allowed to survive to complete 7 months on a carcinogen-free diet, a 5-fold higher TI was recorded. DEN animals treated for 6 months (TI 6.9) but allowed to survive 3 additional months had a TI of 9.6. A similar TI, namely 9.7, was found when the carcinogen-free interval was prolonged for 6 more months. These results suggest that clones of esophageal cells are "programmed" for tumor growth at an early stage of DEN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)