Nitrosation of dietary myosmine as risk factor of human cancer.
The tobacco alkaloid myosmine was detected in nut and nut products [J. Agric. Food Chem. 46 (1998) 2703]. Upon nitrosation, myosmine yields 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and N-nitrosonornicotine (NNN) [J. Agric. Food Chem. 48 (2001) 392]. NNN is a strong oesophageal carcinogen in rats. Metabolic activation of NNN leads to formation of DNA and protein adducts which release HPB upon hydrolysis. In the present study the time, pH and dose-dependent nitrosation of myosmine and its covalent binding to DNA was investigated. [5-(3)H]myosmine was incubated with nitrite for 1-24 h in buffer solutions adjusted to pH 1-6. At pH 2-4 myosmine was easily nitrosated and gave rise to two major products, HPB and NNN, and five minor not yet identified products. Maximal formation was achieved for HPB at pH 2 after 8 h (72% of total radioactivity) and for NNN at pH 3 after 8 h (16%). For DNA binding studies labeled myosmine was incubated under nitrosation conditions with calf thymus DNA. Within 3 h up to 0.1% of the radioactivity was covalently bound to DNA. Endogenous nitrosation of myosmine, present in nuts and other dietary components could constitute a significant risk factor for tumours in the upper intestinal tract such as oesophageal adenocarcinoma, which are unrelated to tobacco smoking and alcohol abuse.
Wilp
J
J
Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University, Nussbaumstrasse 26, D-80336, Munich, Germany.
Zwickenpflug
W
W
Richter
E
E
D000230:Adenocarcinoma / Q000139:chemically induced*; D000470:Alkaloids / Q000378:metabolism*; D002074:Butanones / Q000378:metabolism* / Q000633:toxicity; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009602:Nitrosamines / Q000378:metabolism* / Q000633:toxicity; D015538:Nitrosation; D009754:Nuts / Q000737:chemistry; D011725:Pyridines / Q000378:metabolism* / Q000633:toxicity; D012307:Risk Factors; D013997:Time Factors; D014026:Nicotiana
D000470:Alkaloids; D002074:Butanones; D018736:DNA Adducts; D009602:Nitrosamines; D011725:Pyridines; C074143:4-hydoxy-1-(3-pyridyl)-1-butanone; C002398:myosmine; C008655:N'-nitrosonornicotine