Acute inhibition of DNA synthesis in hamster buccal pouch epithelium exposed to indirect acting carcinogens.
Inhibition of DNA synthesis was observed and quantitated in hamster buccal pouch epithelium exposed in vivo and in vitro to indirect acting carcinogens. Topical application of a 0.5% solution of the potent hamster buccal pouch carcinogen 7,12-dimethylbenz[a]-anthracene (DMBA) acutely inhibited epithelial DNA synthesis by 40-65%, as indicated by a decrease in [3H]thymidine incorporation over a period of 24 h. When applied twice at a concentration of 2%, N-methyl-N-benzylnitrosamine (MBN), another potent buccal pouch carcinogen, inhibited epithelial DNA synthesis by 76% within a period of 4 h. A similar acute inhibitory effect on DNA synthesis was observed when explants of buccal pouch mucosa, exhibiting continuous cell replication, were exposed in vitro in the presence of MBN or DMBA for periods up to 12 and 24 h, respectively. The inhibitory effect of DMBA was greater than that of other polycyclic aromatic hydrocarbons of lesser carcinogenic potency in this tissue. This study demonstrates that the metabolic activation of indirect acting carcinogens leading to acute cytotoxicity and inhibition of DNA synthesis occurs rapidly in hamster buccal pouch mucosa exposed to these agents in vitro as well as in vivo. The experimental imposition of an acute inhibitory pressure, applied as demonstrated in this report, may enable the detection of precancerous cells which have acquired the property of resistance to this cytotoxic effect in the course of carcinogenesis. In principle, the in vitro approach, coupled with autoradiography, may be useful in identifying microscopic foci of resistant preneoplastic cells in samples of human oral mucosa. 24R01 34160
Nagabhushan
M
M
Department of Pathology, Northwestern University, Chicago, IL 60611.
Ng
Y K
YK
Elias
R
R
Polverini
P J
PJ
Solt
D B
DB
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis*; D004128:Dimethylnitrosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D008748:Methylcholanthrene / Q000494:pharmacology; D009061:Mouth Mucosa / Q000166:cytology* / Q000473:pathology; D009336:Necrosis; D013997:Time Factors
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; C014707:nitrosobenzylmethylamine; C030935:benz(a)anthracene; D004128:Dimethylnitrosamine