The role of N-(nitrosomethylamino)propionitrile in betel-quid carcinogenesis.
N-(Nitrosomethylamino)propionitrile (NMAP) was isolated and identified in the saliva of betel-quid chewers in amounts ranging from 0.5 to 11.4 micrograms/l. Groups of 21 male and 21 female rats were given 60 subcutaneous injections of NMAP over a 20-week period (total doses, 0.055 and 0.23 mmol/rat). After 106 weeks, the higher dose had induced 18 (86%) malignant tumours of the nasal cavity in male and 15 (71%) in female rats. Nine (43%) liver tumours were observed among animals treated with the lower dose. Fischer 344 rats were treated with a single dose of NMAP (intravenously or subcutaneously, 0.4 mmol/kg; or by swabbing the oral cavity, 2.21 mmol/kg), and the levels of N7-methylguanine (7-meG) and O6-methylguanine (O6-meG) were measured in DNA isolated from oesophagus and nasal mucosa, which are target organs, and from liver which is not. Higher levels of O6-meG and 7-meG were detected in the nasal mucosa and lesser DNA methylation in the liver and oesophagus, independent of the mode of administration. This correlates with the results of the study of the tumorigenic properties of NMAP in rats.
Prokopczyk
B
B
Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, NY 10595.
Brunnemann
K D
KD
Bertinato
P
P
Hoffmann
D
D
D000478:Alkylation; D000818:Animals; D001114:Areca; D002273:Carcinogens / Q000032:analysis* / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000633:toxicity*; D010946:Plants, Medicinal; D051381:Rats; D011916:Rats, Inbred F344; D012463:Saliva / Q000032:analysis*
D002273:Carcinogens; D009602:Nitrosamines; C042162:3-(methylnitrosamino)propionitrile; D004247:DNA