Sequential histological studies of rat oesophagus during the rapid initiation of cancer by repeated injection of N-methyl-N-benzylnitrosamine.
The sequence of histological changes leading to oesophageal cancer in animals after treatment with various nitrosamines has been studied previously using systems which induced cancer relatively slowly. The more potent carcinogen, N-methyl-N-benzylnitrosamine (MBzN), has been employed to induce cancer in a very much shorter time in experiments designed to detect factors which may potentiate oesophageal cancer. MBzN injected twice weekly for 4 weeks induces papillomas by 4 weeks and carcinomas by 9 weeks. The histological events occurring during the 4-week treatment period have been studied. Initially there was an increase in mitosis. After the second injection, destruction of basal cells occurred, with their complete disappearance from stretches of the epithelium, accompanied by a massive influx of inflammatory cells, and disruption of the normal architecture of the oesophageal epithelium. After 1-2 weeks the numbers of inflammatory cells decreased, concurrently with basal cell hyperplasia and dysplasia, where replicating basal cells penetrated down into the submucosa and upwards towards the lumen. Thickening of the spinous and granular layers of the epithelium and hyperkeratosis were evident, and after 30 days a macroscopically visible papilloma was present. It therefore appears that resistance develops to the toxic inhibitory effect of the carcinogen, and this allows the abnormal replication of basal cells to occur even in the continued presence of the carcinogen. The biochemical processes underlying this development of resistance are being studied, and the effects of possible potentiating factors on the sequence of events occurring during carcinogenesis are being used to test for dietary factors which may enhance oesophageal cancer.
D000818:Animals; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology*; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives*; D004938:Esophageal Neoplasms / Q000139:chemically induced / Q000473:pathology*; D005260:Female; D010212:Papilloma / Q000139:chemically induced / Q000473:pathology; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D002273:Carcinogens; C014707:nitrosobenzylmethylamine; D004128:Dimethylnitrosamine