Tucker J D, Carrano A V, Allen N A, Christensen M L, Knize M G, Strout C L, Felton J S
Biomedical Sciences Division, Lawrence Livermore National Laboratory, CA 94550.
Mutat Res. 1989 Sep;224(1):105-13. doi: 10.1016/0165-1218(89)90009-8.
Using a variety of in vivo cytogenetic endpoints, we have investigated the effects of several compounds formed during the cooking of meat. C57Bl/6 mice were used to test for an increase in the frequency of sister-chromatid exchanges (SCEs), chromosomal aberrations, and micronucleated erythrocytes by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx). 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). MeIQx and DiMeIQx did not induce SCEs in mouse bone marrow cells. PhIP induced sister-chromatid exchanges, but not chromosomal aberrations in bone marrow. In peripheral blood lymphocytes, PhIP did induce aberrations at 100 mg/kg, the highest dose tested. PhIP induced a low but significantly increased frequency of micronuclei in normochromatic but not polychromatic erythrocytes in bone marrow and peripheral blood. However, dose responses were not observed. With the exception of the SCEs induced by PhIP, these results contrast with observations made in vitro, where these compounds were found to have significant genotoxicity in mammalian cells and a very high mutation frequency in prokaryotic systems.
我们使用了多种体内细胞遗传学终点,研究了肉类烹饪过程中形成的几种化合物的影响。利用C57Bl/6小鼠来检测2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉(MeIQx)、2-氨基-3,4,8-三甲基咪唑并[4,5-f]喹喔啉(DiMeIQx)和2-氨基-1-甲基-6-苯基咪唑并[4,5-b]吡啶(PhIP)对姐妹染色单体交换(SCE)频率、染色体畸变和微核红细胞频率的增加情况。MeIQx和DiMeIQx未在小鼠骨髓细胞中诱导SCE。PhIP诱导了姐妹染色单体交换,但未在骨髓中诱导染色体畸变。在外周血淋巴细胞中,PhIP在100mg/kg(测试的最高剂量)时确实诱导了畸变。PhIP在骨髓和外周血的正染色红细胞而非多染色红细胞中诱导了低频率但显著增加的微核。然而,未观察到剂量反应。除了PhIP诱导的SCE外,这些结果与体外观察结果形成对比,在体外研究中发现这些化合物在哺乳动物细胞中具有显著的遗传毒性,在原核系统中具有非常高的突变频率。