methylnitronitrosoguanidine and Carcinoma--Basal-Cell

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.

Topics: Animals; Bromodeoxyuridine; Butylated Hydroxyanisole; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cell Differentiation; Cell Transformation, Neoplastic; Gastric Mucosa; Hyperplasia; Image Processing, Computer-Assisted; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred F344; Stomach; Stomach Neoplasms

Previous studies of chromosome stability in the nevoid basal cell carcinoma syndrome have yielded inconsistent results and suffered from small sample sizes and less than optimal controls. We investigated chromosome fragility and sister chromatid exchange in 20 affected individuals from five multiplex pedigrees, and 15 first- or second-degree unaffected relatives. The percentage of case and control cells showing breaks or rearrangements was compared using a test of proportions. A similar procedure was used to compare site-specific sister chromatid exchanges in baseline cultures from affected persons and controls. No significant differences were noted for either chromosome fragility or sister chromatid exchange between the two groups. These results suggest that cancer susceptibility in the nevoid basal cell carcinoma syndrome is not caused by or manifested as chromosome instability.

Topics: 4-Nitroquinoline-1-oxide; Adult; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Cells, Cultured; Chromosome Fragility; Female; Humans; Lymphocytes; Male; Methylnitronitrosoguanidine; Middle Aged; Mitomycin; Mitomycins; Sister Chromatid Exchange

The skin of white outbred rats was painted with solutions of N-methyl-N-nitrosourea (MNU), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N,N'-dinitroguanidine and diazoacetic ester (DAAE). DAAE was administered to rats intravenously, intraperitoneally and subcutaneously as well. Skin tumours have appeared only in the experiments with MNU, MNNG and DAAE. The application of MNU and MNNG caused tumours of the skin in the site of application, and as for DAAE, it induced tumours in the remote places of the skin. Systemic methods of DAAE administration entailed mainly mammary tumours in female rats, but not those of the skin. Possible mechanisms of action of the compounds under study have been discussed.

Topics: Administration, Topical; Animals; Carcinoma, Basal Cell; Diazonium Compounds; Female; Guanidines; Injections, Intraperitoneal; Injections, Intravenous; Injections, Subcutaneous; Lung Neoplasms; Male; Methylnitronitrosoguanidine; Methylnitrosourea; Nitroso Compounds; Rats; Sarcoma, Experimental; Skin Neoplasms