Acceleration of epithelial keratinization by carcinogens in fetal rat forestomach in organ culture.
Epithelial keratinization in fragments of fetal rat forestomach in organ culture was significantly accelerated by treatment with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 1 h (Fukamachi and Takayama 1979). In this paper, we examined whether acceleration of epithelial keratinization may be characteristic for some carcinogens, and also the mechanism of acceleration of epithelial keratinization by treatment with MNNG. Forestomach epithelial keratinization was accelerated by treatments with 4-nitroquinoline-1-oxide, N-acetoxy-2-acetylaminofluorene, 1-methyl-1-nitrosourea, 7,12-dimethylbenzanthracene, methyl methanesulfonate, and MNNG, but not with 2-acetylaminofluorene, pyrene, or dimethylsulfoxide, indicating that carcinogens may specifically accelerate epithelial keratinization. Chemicals that accelerated epithelial keratinization inhibited epithelial mitotic activity on day 1 in culture, but the mitotic rate was restored to the control level from day 2 onwards. The epithelial keratinization was completely inhibited by adding 5 micrograms/ml of retinoic acid (RA) to the culture medium, irrespective of treatment with MNNG. Addition of 1 microgram/ml of RA suppressed epithelial keratinization in control explants more than in MNNG-treated explants. One possible explanation is that the epithelial cells become less sensitive to RA after MNNG-treatment. A mechanism is proposed assuming that carcinogens induce some qualitative changes in epithelial cells by inhibiting cell proliferation on day 1 in culture, and consequently the epithelial keratinization is accelerated.
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D007633:Keratins / Q000378:metabolism*; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D009924:Organ Culture Techniques; D051381:Rats; D011916:Rats, Inbred F344; D013270:Stomach / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology
D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D015112:4-Nitroquinoline-1-oxide; D014212:Tretinoin; D015127:9,10-Dimethyl-1,2-benzanthracene; D000099:Acetoxyacetylaminofluorene; D007633:Keratins; D008770:Methylnitrosourea; D008741:Methyl Methanesulfonate