限量饮食对化学致癌物-DNA加合物生成的影响

The effect of dietary restriction on the formation of carcinogen DNA adducts

用黄曲霉毒素Ｂ１（ＡＦＢ１）、苯并（ａ）芘（ＢａＰ）和２－乙基氨基芴（２－ＡＡＦ）作为致癌物代表，研究限量饮食（Ｄｉｅｔａｒｙｒｅｓｔｒｉｃｔｉｏｎ，ＤＲ）对雄性Ｆ３４４大鼠和Ｂ６Ｃ３Ｆ１小鼠代谢活化致癌物的影响。以几种致癌物主要的ＤＮＡ加合物作为代谢活化的生物指标。结果显示：限量饮食降低大鼠和小鼠的体重，降低ＡＦＢ１－ＤＮＡ加合物（ＡＤＡ）的生成，增加ＡＦＢ１－谷胱甘肽结合物（ＡＦＢ１－ＳＧ）的生成，增加ＢａＰ－ＤＮＡ加合物（Ｂｐ－Ｎ２－ｄＧ）的生成，但对２－ＡＡＦ－ＤＮＡ加合物（ＡＦ－Ｃ８－ｄＧ）的作用有双重性，染毒后２４，４８小时ＡＦ－Ｃ８－ｄＧ在两组动物肝中无差别，而７２小时后则明显降低ＡＦ－Ｃ８－ｄＧ的生成。结果说明：对于不同的致癌物，ＤＲ有选择性改变代谢酶活性的作用。

Using aflatoxin B 1(AFB 1), benzo a pyrene(BaP) and 2 acetylaminofluorene(2 AAF) as the model indirect acting chemical carcinogens, we have studied the effect of dietary restriction (DR) on metabolic activation of carcinogens in Fischer 344 rats and B6C3F 1 mice. The formation of carcinogen DNA adducts was used as the biomarker of metabolic activiation. The results showed that DR altered the body weight as well as specific carcinogen DNA adducts. Rats and mice had body weights lower than the corresponding controls. DR decreased the formation of two specific AFB 1 DNA adducts, AFB 1 N 7 dG and AFB 1 FAP. The formation of AFB 1 gluathione conjugate (AFB 1 SG) was increased significantly by DR modulation. DR enhanced the total binding of BaP DNA adduct as well as the specific BaP DNA adduct, Bp N 2 dG. The removal of AF C 8 dG from mouse liver DNA showed bi phase curve. The level of the specific 2 AAF DNA adduct, AF C 8 dG, formed in mice 24 and 48h after dosing was not affected by DR. However, 72h after dosing, the AF C 8 dG adduct remaining in mouse liver was lower in DR groups than in AL groups. Our results indicated that the effect of DR on metabolic activation of chemical carcinogen was dependent upon the selected xenobiotic metabolizing enzymes. The change of carcinogen metabolic activation modulated by DR may play an important role in the initiation stage of carcinogenesis.