Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
Dose Response. 2007 Jun 4;5(2):131-49. doi: 10.2203/dose-response.05-037.Scott.
A low-dose protective apoptosis-mediated (PAM) process is discussed that appears to be turned on by low-dose gamma and X rays but not by low-dose alpha radiation. PAM is a bystander effect that involves cross-talk between genomically compromised [e.g., mutants, neoplastically transformed, micronucleated] cells and nongenomically compromised cells. A novel neoplastic cell transformation model, NEOTRANS(3), is discussed that includes PAM. With NEOTRANS(3), PAM is activated by low doses and inhibited by moderate or high doses and is, therefore, a hormetic process. A low-dose region of suppression of the transformation frequency below the spontaneous frequency relates to the hormetic zone over which PAM is presumed to operate. The magnitude of suppression relates to what is called the hormetic intensity. Both the hormetic intensity and width of the hormetic zone are expected to depend on dose rate, being more pronounced after low dose rates. It is expected that PAM likely had a significant role in the following observations after chronic irradiation: (1) what appears to be a tremendous reduction in the cancer incidence below the spontaneous level for Taiwanese citizens residing for years in cobalt-60 contaminated apartments; and (2) the published reductions in the lung cancer incidence below the spontaneous level in humans after protracted X irradiation and after chronic gamma plus alpha irradiation. Implications of PAM for cancer prevention and low-dose cancer therapy are briefly discussed.
一种低剂量保护性细胞凋亡介导(PAM)过程被讨论,这种过程似乎可以被低剂量伽马射线和 X 射线触发,但不能被低剂量的阿尔法射线触发。PAM 是一种旁观者效应,涉及基因组受损的细胞(如突变体、癌变转化、微核化细胞)和非基因组受损细胞之间的串扰。讨论了一种新的肿瘤细胞转化模型 NEOTRANS(3),它包含 PAM。在 NEOTRANS(3)中,PAM 被低剂量激活,被中高剂量抑制,因此是一种适应原性过程。低于自发频率的转化频率的抑制区域与假定 PAM 作用的适应原区域相关。抑制的幅度与所谓的适应原强度有关。适应原强度和适应原区域的宽度都预计取决于剂量率,在低剂量率后更为明显。人们预计 PAM 在以下慢性照射后的观察中可能发挥了重要作用:(1) 台湾居民多年居住在钴-60污染的公寓中,癌症发病率似乎比自发水平低得多;(2) 在慢性伽马射线加阿尔法射线照射后,人类肺癌发病率低于自发水平的公布降低。简要讨论了 PAM 在癌症预防和低剂量癌症治疗中的应用。