STUDY OF TOBACCO CARCINOGENESIS .16. TOBACCO-SPECIFIC NITROSAMINES - FORMATION FROM NICOTINE INVITRO AND DURING TOBACCO CURING AND CARCINOGENICITY IN STRAIN A MICE

STUDY OF TOBACCO CARCINOGENESIS .16. TOBACCO-SPECIFIC NITROSAMINES - FORMATION FROM NICOTINE INVITRO AND DURING TOBACCO CURING AND CARCINOGENICITY IN STRAIN A MICE
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DOI:
10.1093/jnci/60.4.819
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发表时间:
1978-01-01
影响因子:
10.3
通讯作者:
HOFFMANN, D
HOFFMANN, D
中科院分区:
医学1区
文献类型:
--
作者:
HECHT, SS;CHEN, CB;HOFFMANN, D

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研究了烟草生物碱烟碱形成烟草特有亚硝胺的过程。离体叶烟饲喂[2”-14 C]尼古丁或[2”-14 C]去甲尼古丁并晾制。分析烘烤的叶的[2“-14 C] N”-亚硝基去甲烟碱([2“-14 C]NNN)。[2“-14 C]NNN的产率由去甲烟碱和烟碱分别为0.007%和0.009%。由于传统尼古丁型烟草中尼古丁与去甲尼古丁的比例为20-100:1,因此尼古丁被认为是烟草中致癌物NNN的主要前体。研究了尼古丁在体外形成其他亚硝胺的情况。尼古丁与NaNO_2反应生成NNN和另外两种亚硝胺:4-(N-甲基-N-亚硝胺基)-1-(3-吡啶基)-1-丁酮(NNK)和4-(N-甲基-N-亚硝胺基)-4-(3-吡啶基)丁醛(NNA)。对市场产品的分析揭示了NNK(0.6-2.4 μ g/g)在嚼烟和鼻烟中的存在。研究了NNN、NNK和NNA对A系小鼠的致瘤活性。NNK比NNN每只小鼠诱导更多的肺腺瘤,而NNA比NNN活性低。NNN实验组中发生了两例未分化的涎腺癌。
The formation of tobacco-specific nitrosamines from the major tobacco alkaloid nicotine was examined. Detached leaf tobacco was fed [2''-14C]nicotine or [2''-14C]nornicotine and air cured. The cured leaf was analyzed for [2''-14C]N''-nitrosonornicotine ([2''-14C]NNN). The yield of [2''-14C]NNN was 0.007% from nornicotine and 0.009% from nicotine. Because the ratio of nicotine to nornicotine in conventional nicotine-type tobacco is 20-100:1, nicotine is considered to be the major precursor for the carcinogen NNN in tobacco. The formation of other nitrosamines from nicotine in vitro was studied. Reaction of nicotine with NaNO2 gave rise to NNN, and 2 other nitrosamines, 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(N-methyl-N-nitrosamino)-4-(3-pyridyl)butanal (NNA). Analysis of market products revealed the presence of NNK (0.6-2.4 .mu.g/g) in chewing tobacco and snuff. The tumorigenic activity of NNN, NNK and NNA in strain A mice was studied. NNK induced more lung adenomas per mouse than NNN, whereas NNA was less active than NNN. Two cases of undifferentiated carcinoma of the salivary glands occurred in the NNN experimental groups.