Dunn B P
British Columbia Cancer Research Center, Vancouver, Canada.
Environ Health Perspect. 1991 Jan;90:111-6. doi: 10.1289/ehp.90-1519488.
A large variety of environmental carcinogens are metabolically activated to electrophilic metabolites that can bind to nucleic acids and protein, forming covalent adducts. The formation of DNA-carcinogen adducts is thought to be a necessary step in the action of most carcinogens. Recently, a variety of new fluorescence, immunochemical, and radioactive-postlabeling procedures have been developed that allow the sensitive measurement of DNA-carcinogen adducts in organisms exposed to environmental carcinogens. In some cases, similar procedures have been developed for protein-carcinogen adducts. In an organism with active metabolic systems for a given carcinogen, adducts are generally much longer lived than the carcinogens that formed them. Thus, the detection of DNA- or protein-carcinogen adducts in aquatic foodstuffs can act as an indicator of prior carcinogen exposure. The presence of DNA adducts would, in addition, suggest a mutagenic/carcinogenic risk to the aquatic organism itself. Vertebrate fish are characterized by high levels of carcinogen metabolism, low body burdens of carcinogen, the formation of carcinogen-macromolecule adducts, and the occurrence of pollution-related tumors. Shellfish, on the other hand, have low levels of carcinogen metabolism, high body burdens of carcinogen, and have little or no evidence of carcinogen-macromolecule adducts or tumors. The consumption of carcinogen adducts in aquatic foodstuffs is unlikely to represent a human health hazard. There are no metabolic pathways by which protein-carcinogen or DNA-carcinogen adducts could reform carcinogens. Incorporation via salvage pathways of preformed nucleoside-carcinogen adducts from foodstuffs into newly synthesized human DNA is theoretically possible.(ABSTRACT TRUNCATED AT 250 WORDS)
多种环境致癌物经代谢激活后可转化为亲电代谢物,这些代谢物能与核酸和蛋白质结合,形成共价加合物。DNA - 致癌物加合物的形成被认为是大多数致癌物发挥作用的必要步骤。最近,已开发出多种新的荧光、免疫化学和放射性后标记程序,可用于灵敏检测暴露于环境致癌物的生物体中的DNA - 致癌物加合物。在某些情况下,也开发了类似的用于检测蛋白质 - 致癌物加合物的程序。在具有针对特定致癌物的活跃代谢系统的生物体中,加合物的寿命通常比形成它们的致癌物长得多。因此,检测水产食品中的DNA或蛋白质 - 致癌物加合物可作为先前致癌物暴露的指标。此外,DNA加合物的存在表明对水生生物本身存在诱变/致癌风险。脊椎动物鱼类的特点是致癌物代谢水平高、体内致癌物负荷低、形成致癌物 - 大分子加合物以及出现与污染相关的肿瘤。另一方面,贝类的致癌物代谢水平低、体内致癌物负荷高,几乎没有或没有致癌物 - 大分子加合物或肿瘤的证据。食用水产食品中的致癌物加合物不太可能对人类健康构成危害。蛋白质 - 致癌物或DNA - 致癌物加合物不存在能重新形成致癌物的代谢途径。理论上,通过补救途径将食品中预先形成的核苷 - 致癌物加合物掺入新合成的人类DNA中是可能的。(摘要截取至250字)