Persistent infections and their relationship with selected oncologic and non-tumor pathologies.

Our earlier studies of hepatitis C virus (HCV) infection rates among blood donors at the Kyiv Municipal Blood Center revealed a 3.45% HCV+ prevalence in these "healthy" hosts. In the study here, we analyzed HCV (as well as cytomegalovirus [CMV]) prevalence among Chernobyl nuclear power plant (NPP) accident sufferers--cleanup workers, local residents, NPP workers, and convalescent patients--who suffered acute radiation syndrome (ARS) as a result of the 1986 accident, and individuals who had not been exposed to ionizing radiation (IR). Serological analyses of antibodies against each pathogen (via enzyme-linked immunosorbent assay [ELISA]) revealed the highest HCV (i.e., 27.2%) and CMV (85.6%) prevalence in the convalescent hosts. Though the HCV prevalence (reflecting a current/past infection) among the cleanup workers (and other groups) was lower (i.e., 11-25%), viral presence was "associated" with a higher incidence of selected somatic diseases, for example, thyroiditis, goiter, hypertension, Type 1 diabetes, chronic hepatitis/gastritis, in the cleanup workers. A similar scenario with respect to CMV was also seen, i.e., lower prevalence rates [relative to in ARS patients] and "association" between CMV status and incidence of chronic gastritis, arthritis, and bronchitis, in the cleanup workers and IR-non-exposed controls. Further, irrespective of CMV status, there was a clear delineation between incidence rate(s) of each of the pathologies and whether or not the person was/was not exposed in 1986. We also investigated, due to a high incidence of chronic lymphocytic leukemia (CLL) among Chernobyl sufferers, if there was homology between immunoglobulins (Igs) generated by these transformed cells and known antiviral and antimicrobial Igs. Polymerase chain reaction (PCR) analyses of Ig heavy-chain variable (IgHV) genes in cells from CLL patients who were/were not exposed in 1986 revealed a significant homology of some IgHV genes with Igs directed against infectious agents. However, no differences were found between the sequences from IR-exposed and IR-non-exposed CLL patients. Based on the findings here, we conclude that a past/ongoing presence of certain viral infections (i.e., CMV and/or HCV) in a host can modify (aggravate) the clinical course of certain somatic (i.e., non-tumor) diseases and promote malignancies (i.e., CLL), and that each of these outcomes could be modulated as a result of that host's past exposure to IR.

MLL gene alterations in radiation-associated acute myeloid leukemia.

AIM: Although acute myelogenous leukemia (AML) arising after radiation exposure is considered to be secondary, little is known about the molecular mechanisms by which the radiation induces the leukemogenic phenotype. The aim of the study was to analyze whether the MLL translocations are as frequent in radiation-associated AML as in spontaneous AML cases. METHODS: Sixty one AML samples obtained at diagnosis were analyzed for the presence of MLL abnormalities using fluorescent in situ hybridization and/or reverse transcription polymerase chain reaction. Of these patients, 27 had experienced radiation exposure due to the Chernobyl accident, 32 were non-irradiated (spontaneous AML), and 2 developed therapy-related AML after chemotherapy with topoisomerase II inhibitors. RESULTS: MLL gene translocations were detected in both groups of spontaneous and therapy-related AML (1/32 and 1/2 cases respectively). The sole MLL rearrangement found in the group of radiation-associated AML patients was a duplication of the gene. CONCLUSION: Our data preclude the involvement of MLL gene translocations in radiation-induced leukemogenesis, but support the assumption that loss and gain of chromosomal material could be crucial in the leukemogenesis of AML patients with the history of radiation exposure due to the Chernobyl accident.