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N-苯基-2-萘胺(P2NA)和 N-苯基-1-萘胺(P1NA)主要用作橡胶制品的抗氧化剂。由于它们对大小鼠诱发癌症而引起各界对深入研究其代谢和致癌机理的重视。芳香胺类致癌物的代谢是通过羟化酶、偶氮还原酶、去甲基酶等而实现,其中尤以羟化酶较为重要。大多数致癌性芳香胺及酰胺都是通过N-羟基化而激活,生成最终致癌物。但我们在用新鲜分离的肝细胞作P2NA和P1NA体外代谢时,其主要产物首先为环氧化物,再进一步生成酚类化合物。环氧化物具有较强的使细胞恶性转化的能力,因其与核酸、蛋白质的结合较强,并具有致突变作用,因而认为环氧化物可能是某些致癌物的最终致癌物。而环羟基化的生物转化可能是解毒作用。本文研究了P2NA和P1NA的大鼠体内代谢,旨在与用大鼠肝细胞的体外代谢转化过程作比较,进一步阐明它们的致癌机理。
N-phenyl-2-naphthylamine (P2NA) and N-phenyl-1-naphthylamine (P1NA) are mainly used as antioxidants for rubber products. Due to their induction of cancer in large mice, all walks of life have drawn attention to the in-depth study of their metabolic and carcinogenic mechanisms. The metabolism of aromatic amine carcinogens is achieved by hydroxylases, azoreductases, demethylases, etc., among which hydroxylases are particularly important. Most carcinogenic aromatic amines and amides are activated by N-hydroxylation to produce the ultimate carcinogen. However, when we use freshly isolated hepatocytes to metabolize P2NA and P1NA in vitro, the main product is epoxide first, and further phenolic compounds are generated. Epoxide has a strong ability to malignant transformation of cells, because of its strong binding to nucleic acids and proteins, and has a mutagenic effect, so that epoxides may be the ultimate carcinogen of some carcinogens. The biotransformation of cyclohydroxylation may be detoxification. This study investigated the in vivo metabolism of P2NA and P1NA in rats and compared them with the in vitro metabolic transformation of rat hepatocytes to further elucidate their carcinogenic mechanisms.