Approaches to the development of assays for interaction of tobacco-specific nitrosamines with haemoglobin and DNA.
The tobacco-specific, nicotine-derived nitrosamines 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) are among the most important carcinogens in tobacco and tobacco smoke. Treatment of Fischer 344 rats with these carcinogens resulted in alkylation of haemoglobin and DNA by the 4-(3-pyridyl)-4-oxobutyl group formed during their metabolism. This alkyl group can be detached from globin or DNA under mild hydrolytic conditions as 4-hydroxy-1-(3-pyridyl)-1-butanone, which appears to be a potentially useful dosimeter for human exposure to, and activation of, tobacco-specific nitrosamines.
Hecht
S S
SS
American Health Foundation, Valhalla, NY.
Carmella
S G
SG
Trushin
N
N
Spratt
T E
TE
Foiles
P G
PG
Hoffmann
D
D
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004784:Environmental Monitoring; D006454:Hemoglobins / Q000378:metabolism*; D009602:Nitrosamines / Q000378:metabolism*; D010947:Plants, Toxic; D051381:Rats; D011916:Rats, Inbred F344; D012906:Smoke / Q000032:analysis; D014026:Nicotiana / Q000032:analysis
D002273:Carcinogens; D006454:Hemoglobins; D009602:Nitrosamines; D012906:Smoke; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D004247:DNA; C008655:N'-nitrosonornicotine