Reversibility of carcinogen-induced rat forestomach basal cell hyperplasia is due to squamous cell differentiation.
The mechanisms of reversibility of basal cell hyperplasia in the rat forestomach were investigated. Male F344 rats were given an initial single gastric intubation of N-methyl-N'-nitro-N-nitorosoguanidine and then received 2% butylated hydroxyanisole in the diet from the third week to the 26th week. Rats were killed at weeks 26 and 46 after return to basal diet and their forestomachs were removed. Bromouracil deoxyriboside (BUdR) was administered as a single i.p. injection 1 h before death or by osmotic minipump (120 micrograms/h) continuously for 7 days before death. Additional animals were maintained for 2 or 4 weeks after removal of osmotic minipumps to allow assessment of the fate of proliferating populations. In each case BUdR-labeled cells were demonstrated by immunohistochemistry by immunohistochemistry. At week 26, hyperplastic changes were more pronounced than at week 46. Squamous cells above basal cell hyperplasias were strongly labeled even 4 weeks after cessation of continuous BUdR Three-dimensional reconstruction of persisting basal cell hyperplasias showed almost all basal cells limited to a thin sheet in direct contact with the squamous cell layer, occasional separate islands demonstrating differentiation to squamous cells and formation of epidermal cysts. The results thus showed that the mechanism of reversibility of basal cell hyperplasia involves differentiation of basal cells to squamous cells.
Ogawa
K
K
First Department of Pathology, Nagoya City University Medical School.
Hoshiya
T
T
Kato
T
T
Shirai
T
T
Tatematsu
M
M
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002083:Butylated Hydroxyanisole; D002280:Basal Cell Carcinoma / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D005753:Gastric Mucosa / Q000378:metabolism; D006965:Hyperplasia / Q000139:chemically induced; D007091:Image Processing, Computer-Assisted; D008297:Male; D008769:Methylnitronitrosoguanidine; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000187:drug effects / Q000473:pathology*; D013274:Stomach Neoplasms / Q000473:pathology*
D008769:Methylnitronitrosoguanidine; D002083:Butylated Hydroxyanisole; D001973:Bromodeoxyuridine