The induction of esophageal tumors in mice: dose and time dependency.

Three hundred and forty eight C57Bl mice were killed after diethyl-nitrosamine (DEN) treatment at various time intervals ranging from one day to six months. No esophageal tumors occurred in the first three months after DEN treatment; They occurred, however, at four months and increased in number at six months of DEN treatment. Other groups of animals under the same initial DEN treatment were allowed to survive seven or nine months without treatment. One esophageal tumor was recorded at observations made seven months after one single day of DEN administration. A significant increase in the number of esophageal tumors occurred at seven months in mice treated with DEN for two weeks, and for one, two, three or four months; the highest tumor frequency was found in mice treated for six months and surviving three additional months on a carcinogen-free diet. These results suggest that clones of esophageal cells had been "programmed" for tumor growth at an early stage of DEN treatment. The tumors had, however, remained undetected at macroscopical and microscopical examination several months previously. It is apparent that not only the dose administered, but also the post-carcinogen interval is an important factor in esophageal carcinogenesis in the mouse.