Trosko J E, Chang C C
National Food Safety and Toxicology Center, Department of Pediatrics and Human Development, Michigan State University, East Lansing 48824, USA.
Biofactors. 2000;12(1-4):259-63. doi: 10.1002/biof.5520120139.
Chemopreventive or chemotherapeutic agents have been those that either kill cancer cells to a differential degree over the non-cancer cells or those chemicals that either block the induction of tumors in carcinogen-treated animals or retard transplanted tumors in animals. Carcinogenesis is a multi-stage, multi-mechanism process, involving the irreversible alteration of a stem cell ("initiation"), followed by the clonal proliferation of the initiated cell ("promotion"). To develop a strategy for intervention with chemoprevention/chemotherapeutic chemicals, the basic mechanism(s) of carcinogenesis must be understood. Gap junction intercellular communication (GJIC) regulates cell growth, differentiation, apoptosis and adaptive functions of differentiated cells. Normal cells have functional GJIC while cancer cells do not. Tumor promoters and oncogenes inhibit GJIC, while anti-tumor promoter and anti-oncogene drugs can reverse the down-regulation of GJIC. Transfection of gap junction genes (connexins) has been shown to reverse the tumorigenic phenotype. If prevention/treatment of cancer is to occur, prevention of the chronic down regulation of GJIC by tumor promoters in non-tumorigenic but initiated cells or the up-regulation of GJIC in stably down-regulated GJIC in tumor cells must occur to prevent or to treat cancers.
化学预防剂或化学治疗剂是指那些对癌细胞的杀伤程度高于非癌细胞的物质，或者是那些能够在致癌物处理的动物中阻断肿瘤诱导或延缓动物体内移植肿瘤生长的化学物质。致癌作用是一个多阶段、多机制的过程，涉及干细胞的不可逆改变（“启动”），随后是启动细胞的克隆增殖（“促进”）。要制定化学预防/化学治疗药物的干预策略，必须了解致癌作用的基本机制。间隙连接细胞间通讯（GJIC）调节细胞生长、分化、凋亡以及分化细胞的适应性功能。正常细胞具有功能性GJIC，而癌细胞则没有。肿瘤促进剂和癌基因抑制GJIC，而抗肿瘤促进剂和抗癌基因药物可以逆转GJIC的下调。间隙连接基因（连接蛋白）的转染已被证明可以逆转致瘤表型。如果要预防/治疗癌症，就必须防止肿瘤促进剂在非致瘤但已启动的细胞中对GJIC的慢性下调，或者在肿瘤细胞中稳定下调的GJIC中上调GJIC，以预防或治疗癌症。
