Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation

Dose-dependent effect of dietary meat on endogenous colonic N-nitrosation
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DOI:
10.1093/carcin/22.1.199
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发表时间:
2001-01-01
期刊:
影响因子:
4.7
通讯作者:
Bingham, S
Bingham, S
中科院分区:
医学2区
文献类型:
--
作者:
Hughes, R;Cross, AJ;Bingham, S

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在代谢设施中对人类男性志愿者进行了研究,同时给他们喂食随机控制的饮食。当在 10 天的时间里随机将肉类剂量从 0 增加到 60、240 和 420 克/天时,8 名志愿者的粪便表观总 N-亚硝基化合物 (ATNC) 和亚硝酸盐排泄量显着增加(分别为 P < 0.0001 和 P = 0.046)。当饮食中不含肉类时,平均(+/- SE)粪便 ATNC 水平为 54 +/- 7 克/天;当饮食中含有 60 克肉/天时,粪便 ATNC 水平为 52 +/- 11 杯/天;当饮食中含有 240 克肉时,粪便 ATNC 水平为 159 +/- 33 杯/天;当饮食含有 420 克肉时,粪便 ATNC 水平为 199 +/- 36 杯/天。 NOC 浓度越高,在肠道中的转运时间越长(r = 0.55,P = 0.001)和低粪便重量(r = -0.51,P = 0.004)。在连续 40 天喂食 420 克肉的个体中,该水平没有显着下降。较高肉类饮食中发现的 N-亚硝基化合物 (NOC) 暴露量与烟草烟雾等其他来源的 N-亚硝基化合物 (NOC) 相当。许多 NOC 是结肠癌中已知的大肠启动子和启动子,诱导 K-ras 密码子 12 和 13 中的 G→A 转变,内源性 NOC 的形成,加上肠道中较长的转运时间,可以解释高肉/低纤维饮食与结直肠癌风险之间的流行病学关联。
Human male volunteers were studied in a metabolic facility whilst they were fed randomized controlled diets. In eight volunteers there was a significant increase in faecal apparent total N-nitroso compounds (ATNC) and nitrite excretion (P < 0.0001 and P = 0.046, respectively) when randomized doses of meat were increased from 0 to 60, 240 and 420 g/day over 10 day periods. Mean (+/- SE) faecal ATNC levels were 54 +/- 7 g/day when the diets contained no meat, 52 +/- 11 mug/day when the diets contained 60 g meat/ day, 159 +/- 33 mug/day with 240 g meat and 199 +/- 36 mug/ day with 420 g meat, Higher concentrations of NOC were associated with longer times of transit in the gut (r = 0.55, P = 0.001) and low faecal weight (r = -0.51, P = 0.004). There was no significant decline in levels in individuals fed 420 g meat for 40 days. The exposures found on the higher meat diets were comparable with other sources of N-nitroso compounds (NOC), such as tobacco smoke. Many NOC are known large bowel initiators and promoters in colon cancer, inducing G-->A transitions in codons 12 and 13 of K-ras, Endogenous NOC formation, combined with prolonged transit times in the gut, may explain the epidemiological associations between high meat/low fibre diets and colorectal cancer risk.