Clastogenic plasma factors: a short overview

Abstract

A large number of studies have revealed that irradiated subjects produce soluble factors found in their blood plasma which, when transferred into cell cultures from non-irradiated individuals, show clastogenic (chromosome breaking) activity. Increased yields of chromatid-type aberrations have been characteristic in most of these studies. Exposed cohorts of various origins have revealed to possess this feature: from A-bomb survivors to patients treated with radiotherapy. It is apparent that the plasma factors are sustainable for long time periods. On the other hand, they seem to be produced very fast after exposure. Considerable variation in the effect has been found between individuals with similar radiation exposure. Further, the phenomenon is not restricted to irradiated populations. Clastogenic plasma has also been observed in patients with inflammatory diseases or congenital chromosome breakage syndromes as well in subjects exposed to other agents than ionizing radiation. Chromosomal aberration inducing substances have been detected not only in vivo, but also in vitro. A common feature to all the conditions is that they are associated with oxidative stress. Studies on the biochemical nature of the clastogenic factor(s) have been conducted, and tumor necrosis factor alpha and lipid peroxidation products, among others, have been suggested as good candidates. The relevance of the plasma factors to health effects remains open. The aim of the paper is to give a short overview on the phenomenon of clastogenic factors--their occurrence and formation as well as possible effectors.

Oxidative stress in Fanconi anaemia: from cells and molecules towards prospects in clinical management

“…Moreover, TNF-α treatment induces FANCA and FANCG through NF-κ B (Mac é et al, 2007 ). In turn, TNF-α and its interactors are recognized to be involved in a proinfl ammatory/prooxidant condition, thus their roles in FA phenotype point, per se , to the relevance of redox imbalances in FA pathogenesis (Obrador et al , 1998 ;Lindholm et al , 2010 ).…”

Embryos of the zebrafish Danio rerio in studies of non-targeted effects of ionizing radiation

“…In particular, superoxide dismutase (SOD) inhibited the formation of the CF, which indicated the involvement of superoxide radicals in the CF. In contrast, the cytotoxic cytokine tumor necrosis factor-a (TNF-a) and the formation of lipid peroxidation products, as well as the production of free radicals were proposed to be related to the clastogenic activity [37]. Notably, free radical scavengers have been reported to successfully reduce the clastogenic activity in many studies.…”

“…Studies on plasma clastogenic effect were later reviewed by Mothersill and Seymour [2], Goldberg and Lehnert [38], Morgan [49] and Lindholm et al [37]. It would also be interesting and beneficial to study whether the CF can be transmitted at the inter-organismic level.…”

Bystander Signalling: Exploring Clinical Relevance Through New Approaches and New Models

“…These are summarised in table 3. The first in vivo evidence of RIBEs was provided by the identification of cell damaging or clastogenic factors in the serum of irradiated patients which when transferred onto cultures of unirradiated lymphocytes showed cell damaging activity (33,34). As in more simplistic cell models, it is difficult to distinguish between types of radiation induced signalling in vivo.…”