Bartsch H, Malaveille C
International Agency for Research on Cancer, Lyon, France.
Cell Biol Toxicol. 1989 Jun;5(2):115-27. doi: 10.1007/BF00122647.
To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in humans and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and on agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and 3. The results of this analysis indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro/in vivo genotoxicity assays (involving as endpoints DNA damage and chromosomal/mutational damage) may represent a hazard to humans; and b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall, this analysis implies that genotoxic carcinogens add more to the cancer burden in man than non-genotoxic carcinogens. Thus, identification of such genotoxic carcinogens and subsequent lowering of exposure will remain the main goal for primary cancer prevention in man.
为了确定遗传毒性致癌物和非遗传毒性致癌物对人类癌症负担的贡献是否相似，对在《国际癌症研究机构专论》第6卷和第7卷中评估了其对人类和动物致癌作用以及短期遗传毒性试验活性的物质进行了分析。确定了遗传毒性致癌物在四组物质中的流行情况，这四组物质包括已确定的人类致癌物（第1组，n = 30）、可能的人类致癌物（第2A组，n = 37）、可能的人类致癌物（第2B组，n = 113）以及在动物中致癌性证据有限的物质（第3组的一个子集，n = 149）。在第1、2A和2B组中，发现遗传毒性致癌物的流行率高达80%至90%，这些组也被证明是多物种/多组织致癌物。啮齿动物致癌效力的分布并未揭示第1组人类致癌物有任何将它们与第2A、2B和3组物质区分开来的特定特征。该分析结果表明：(a) 一种致癌潜力未知但在体外/体内遗传毒性试验（以DNA损伤和染色体/突变损伤为终点）中显示出充分活性证据的物质可能对人类构成危害；(b) 鉴于目前缺乏针对非遗传毒性致癌物的经过验证的短期试验，一种在该遗传毒性试验范围内显示无活性的物质应通过啮齿动物生物测定法进行致癌性评估。总体而言，该分析表明遗传毒性致癌物对人类癌症负担的增加比非遗传毒性致癌物更多。因此，识别此类遗传毒性致癌物并随后降低暴露水平仍将是人类原发性癌症预防的主要目标。
