限量饮食对致癌物活化代谢及DNA断裂的影响

DIETARY RESTRICTION MODULATED CARCINOGEN METABOLIC ACTIVATION AND THE CARCINOGEN INDUCED DNA STRAND BREAKS

目的：研究限量饮食（ＤＲ）对小鼠肝代谢活化致癌物以及致癌物导致的ＤＮＡ链断裂程度的影响。方法：用３２Ｐ后标记和高效液相色谱法测定致癌物ＤＮＡ主要加合物生成量；用随机寡核甘酸引物合成法（ＲＯＰＳ）测定ＤＮＡ链断裂程度；用体外代谢酶活性测定法检测有关代谢酶的活性。结果：①限量饮食减少小鼠肝中黄曲霉毒素Ｂ１（ＡＦＢ１）和２乙基氨基芴（２ＡＡＦ）ＤＮＡ加合物（ＡＦＣ８ｄＧ）的生成，同时也减少致癌物导致的ＤＮＡ链断裂；限量饮食增加苯并［ａ］芘（ＢａＰ）ＤＮＡ加合物（ＢａＰＮ２ｄＧ）和６硝基苯甲萘（６ＮＣ）ＤＮＡ总加合物的生成，也增加致癌物导致的ＤＮＡ链断裂。②在小鼠肝中，致癌物ＤＮＡ加合物的生成量与致癌物导致的ＤＮＡ链断裂程度密切相关；③限量饮食诱导某些与致癌物代谢有关的酶。结论：限量饮食特异地改变小鼠肝代谢酶的活性继而影响致癌物的代谢活化，这种作用在致癌过程的起始阶段可能起着重要的作用。

Objective: To study the effect of dietary restriction on the metabolic activation of carcinogens and carcinogen induced DNA strand breaks in B6C3F 1 mouse livers. Methods: 32 P postlabelling and HPLC techniques were applied to detect the formation of major carcinogen DNA adducts. Random oligonucleotide primed synthesis was used to measure the extent of DNA strand breaks. The enzyme activity was measured by the in vitro metabolic experiment. Results: To be showed that DR significantly inhibited aflatoxin B 1(AFB 1) DNA major adduct and 2 acetylaminofluorene (2 AAF) DNA major adduct (AF C 8 dG) formation as well as carcinogen induced strand breaks. DR enhanced the formation of hepatic benzopyrene(BaP) DNA adduct (BaP N 2 dG) and total 6 nitrochrysene (6 NC) DNA adducts as well as BaP , 6 NC induced DNA strand breaks. The formation of the carcinogen DNA adduct in mouse liver was correlated with the carcinogen induced DNA strand breaks. DR also induced the activity of several metabolizing enzymes. Conclusion: The effect of DR on the carcinogen activation is dependent upon the DR modulated carcinogen metabolizing enzyme activities. It may play an important role in the initiation stage of carcinogenesis.