The assumption that chemical and radiation induced cancers act in a manner that is additive to background was proposed in the mid-1970s. It was adopted by the U.S. Environmental Protection Agency (EPA) in 1986 and then subsequently by other regulatory agencies worldwide for cancer risk assessment. It ensured that cancer risks at low doses act in a linear fashion. The additive to background process assumes that the mechanism(s) resulting in induced (i.e., treatment related) and spontaneous (i.e., control group) cancers are identical. This assumption could not be properly evaluated due to inadequate mechanistic data when it was proposed in the 1970s. Using the findings of modern molecular toxicology, including oncogene activation/mutation, gene regulation, and molecular pathway analyses, the additive to background assumption was evaluated in the present paper. Based on published studies with 45 carcinogens over 13 diverse mammalian models and for a broad range of tumor types compelling evidence indicates that carcinogen-induced tumors are mediated in general via mechanisms that are not identical to those affecting the occurrence of the same type of spontaneous tumors in appropriate control groups. These findings, which challenge a fundamental assumption of the additive to background concept, have significant implications for cancer risk assessment policy, regulatory agency practices, as well as fundamental concepts of cancer biology.

1970年代中期提出了一种假设，即化学和辐射诱发的癌症以与背景相加的方式起作用。它于1986年被美国环境保护署（EPA）采用，随后又被全球其他监管机构用于癌症风险评估。它确保了低剂量的癌症风险呈线性关系。背景过程的添加剂假定导致诱发（即与治疗有关）和自发性（即对照组）癌症的机制是相同的。由于在1970年代提出的机械数据不足，因此无法正确评估该假设。利用现代分子毒理学的发现，包括致癌基因激活/突变，基因调控和分子途径分析，本文对背景假设进行了评估。基于对13种不同的哺乳动物模型中的45种致癌物进行的公开研究，并针对广泛的肿瘤类型，有力的证据表明，致癌物诱导的肿瘤一般是通过与影响相同类型自发性肿瘤发生的机制不同的机制介导的。在适当的对照组中。这些发现挑战了有关背景概念添加剂的基本假设，对癌症风险评估政策，监管机构的实践以及癌症生物学的基本概念均具有重要意义。基于对13种不同的哺乳动物模型中的45种致癌物进行的公开研究，并针对广泛的肿瘤类型，有力的证据表明，致癌物诱导的肿瘤一般是通过与影响相同类型自发性肿瘤发生的机制不同的机制介导的。在适当的对照组中。这些发现挑战了有关背景概念添加剂的基本假设，对癌症风险评估政策，监管机构的实践以及癌症生物学的基本概念均具有重要意义。基于对13种不同的哺乳动物模型中的45种致癌物进行的公开研究，并针对广泛的肿瘤类型，有力的证据表明，致癌物诱导的肿瘤一般是通过与影响相同类型自发性肿瘤发生的机制不同的机制介导的。在适当的对照组中。这些发现挑战了有关背景概念添加剂的基本假设，对癌症风险评估政策，监管机构的实践以及癌症生物学的基本概念均具有重要意义。