Low-Dose Cancer Risk Modeling Must Recognize Up-Regulation Of Protection

Ionizing radiation primarily perturbs the basic molecular level proportional to dose, with potential damage propagation to higher levels: cells, tissues, organs, and whole body. There are three types of defenses against damage propagation. These operate deterministically and below a certain impact threshold there is no propagation. Physical-static defenses precede metabolic-dynamic defenses acting immediately: scavenging of toxins; - molecular repair, especially of DNA; - removal of damaged cells either by apoptosis, necrosis, phagocytosis, cell differentiation-senescence, or by immune responses, - followed by replacement of lost elements. Another metabolic-dynamic defense arises delayed by up-regulating immediately operating defense mechanisms. Some of these adaptive protections may last beyond a year and all create temporary protection against renewed potentially toxic impacts also from non-radiogenic endogenous sources. Adaptive protections have a maximum after single tissue absorbed doses around 100 to 200 mSv and disappear with higher doses. Low dose rates initiate maximum protection likely at lower cell doses delivered repetitively at certain time intervals. Adaptive protection preventing only about 2 – 3 % of endogenous life-time cancer risk would fully balance a calculated induced cancer risk at about 100 mSv, in agreement with epidemiological data and concordant with an hormetic effect. Low-dose-risk modeling must recognize up-regulation of protection

Lymphohematopoietic malignancies

In this chapter, we present the 2017 revised WHO classification as the current reference standard for lymphohematopoietic malignancies. According to this, we discuss in detail the subgroups of myeloid and lymphoid malignancies, characterizing their biological and clinical features. Then, based on the current list of putative carcinogens maintained by the International Agency for Research on Cancer (updated to November 2018), we describe the possible occupational risk factors for myeloid and lymphoid malignancies. In particular, we focus on ionizing radiations (including fission products, phosphorus-32, strontium-90, thorium-232, and its decay products), benzene, 1,3-butadiene, formaldehyde, two pesticides (lindane and pentachlorophenol), and a generically identified industrial process (rubber production industry). As reviewed in the chapter, the case definitions adopted in epidemiological studies seldom met the classification criteria established by WHO. Hence, knowledge on putative risk factors for lymphohematopoietic malignancies is limited to major groupings, such as non-Hodgkin lymphoma, chronic lymphoid leukemia. Future researches should be oriented to study specific diseases and based on case definitions derived by systematic classifications of lymphohematopoietic malignancies