綜述：馬兜鈴酸的遺傳毒性   全文下載

Genotoxicity of Aristolochic Acid: A Review

馬兜鈴酸存在於很多馬兜鈴科的植物之中，這些植物被廣泛用作草藥治療人類疾病。可是，這些包含馬兜鈴酸的植物產品可產生很強的腎臟毒性、遺傳毒性、以及致癌性。馬兜鈴酸已被証實可誘發大鼠和小鼠腎臟和其它組織器官的腫瘤。因此，含有馬兜鈴酸的植物產品已經被許多國家禁用。在此綜述中，我們總集和分析了可獲得的有關馬兜鈴酸遺傳毒性的文獻和數據，並且歸納和討論了其可能的作用機制。大量數據証實馬兜鈴酸是一個致突變劑。其致突變性主要產生於馬兜鈴酸的dna 加合物。馬兜鈴酸不但可誘發細菌、哺乳動物細胞、果蠅和老鼠的基因突變，產生遺傳毒性，它還可誘發人類腫瘤基因的遺傳突變。此外，馬兜鈴酸還是一個dna 斷裂劑。此遺傳毒性可造成染色体損害、導致基因組的不穩定性，從而加速腫瘤的惡化。這些結果證明馬兜鈴酸是一個誘導遺傳突變的致癌物質。

Aristolochic acid (AA), a mixture of aristolochic acid I (AAI) and aristolochic acid II (AAII), is present in Aristolochiaceae plants, many of which are used as herbal folk remedies. Plants containing AA, however, can be nephrotoxic, genotoxic and carcinogenic in humans. AA has been also associated with the development of tumors in mice and rats. Therefore, plant products containing AA have been banned in many countries. Because quantitative cancer risk assessment is based upon an understanding of the chemical’s mode-of-action, it is necessary to determine whether the chemical is a mutagenic carcinogen. In this review, we present the available information concerning the genotoxicity of AA and discuss the possible mechanisms for mutation induction by AA. The evidences indicate that AA is mutagenic and this activity is mediated mainly by the formation of AA-DNA adducts. Not only does AA induce genetic damage and mutations in bacteria, mammalian cells, Drosophila, and rodents, but it is also demonstrated to induce mutations in the target tissues of the model animals and oncogenes from human. Many evidences from genotoxicity tests also indicate that AA is a clastogenic agent that breaks DNA and results in chromosome damage and chromosome mutations. These results indicate that AA is a mutagenic carcinogen.