Huff J
Environmental Carcinogenesis Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Am J Ind Med. 1995 Feb;27(2):293-300. doi: 10.1002/ajim.4700270213.
Mechanisms of carcinogenesis--and in particular chemically associated carcinogenicity--have attracted considerable scientific and public attention in the last decade. Much insight has been gained that will lead to more reasoned and better prevention, intervention, and treatment for the reduction of environmentally caused cancers. However, there seems to be an exaggerated tendency to embrace "mechanisms" not yet fully characterized, completely tested, unequivocally proven, and consensus accepted. More than 100 agents and exposure circumstances have been identified as causally or strongly associated with human cancers; for many the evidence was discovered first in experimental animals. More chemicals have been uncovered as carcinogenic in experimental animals, with as yet no or little available information in exposed human populations. Additional and expanded mechanistic and epidemiological studies should further elucidate the relevance of these agents to adverse human health effects, including cancers. Claims are being posed that certain chemical-specific "mechanisms" in experimental systems are irrelevant to humans, and thus chemicals thought to be aberrantly carcinogenic in animals would present no cancer hazard to exposed humans. Nonetheless before undeniable proof becomes available, we must continue to proceed with sensitive and responsible caution. This commentary offers a central and personal view of one such mechanism: cell proliferation and cancer.
在过去十年中，致癌机制——尤其是化学相关致癌性——已经引起了科学界和公众的广泛关注。我们已经获得了许多见解，这将有助于采取更合理、更有效的预防、干预和治疗措施，以减少环境因素导致的癌症。然而，对于那些尚未得到充分表征、全面测试、明确证实和普遍认可的“机制”，似乎存在一种过度追捧的倾向。已经确定有100多种物质和暴露情况与人类癌症存在因果关系或密切关联；其中许多证据最初是在实验动物中发现的。在实验动物中发现了更多具有致癌性的化学物质，而在接触这些化学物质的人群中，相关信息却很少或几乎没有。更多深入和扩展的机制研究及流行病学研究应能进一步阐明这些物质与包括癌症在内的人类健康不良影响之间的关联。有人声称，实验系统中某些特定化学物质的“机制”与人类无关，因此，那些在动物身上被认为具有异常致癌性的化学物质不会对接触它们的人类构成癌症风险。尽管如此，在获得确凿证据之前，我们必须继续保持谨慎和负责的态度。本评论提供了关于其中一种机制——细胞增殖与癌症——的核心且个人的观点。
