Frequencies of X-ray induced chromosome aberrations in lymphocytes of xeroderma pigmentosum and Fanconi anemia patients estimated by Giemsa and fluorescence in situ hybridization staining techniques

Abstract

Blood lymphocytes from xeroderma pigmentosum (XP) and Fanconi anemia (FA) patients were assessed for their sensitivity to ionizing radiation by estimating the frequency of X-ray (1 and 2 Gy)-induced chromosome aberrations (CA). The frequencies of aberrations in the whole genome were estimated in Giemsa-stained preparations of lymphocytes irradiated at G 0 or G 2 stages. The frequencies of translocations and dicentrics involving chromosomes 1 and 3 as well as the X-chromosome were determined in slides stained by fluorescence in situ hybridization (FISH) technique. An increase in all types of CA was observed in XP and FA lymphocytes irradiated at G 0 when compared to controls. The frequency of dicentrics and rings was 6 to 27% higher (at 1 and 2 Gy) in XP lymphocytes and 37% higher (at 2 Gy) in FA lymphocytes than in controls, while chromosome deletions were higher in irradiated (30% in 1 Gy and 72% in 2 Gy) than in control XP lymphocytes and 28 to 102% higher in FA lymphocytes. In G 2 -irradiated lymphocytes the frequency of CA was 24 to 55% higher in XP lymphocytes than in controls. In most cases the translocation frequencies were higher than the frequencies of dicentrics (21/19).

The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers

“…Although other types of mutation also create differentiation blocks in AML, the large increases in relative risk in Fanconi anemia suggests that gene rearrangements are important. In Fanconi anemia, translocations occur at a rate that is at least ten times greater than normal after exposure to ionizing radiation [70]. …”

Cytogenetic studies of chromosomal breakage diseases

“…The levels of SCE in patients with XP did not differ markedly from normal (Wolf et al, 1975). However, the level of CAs of lymphocytes exposed to irradiation has shown marked elevation than normal (Saraswathy and Natarajan, 2000). Also, cultured fibroblast exposed to UV has shown elevated levels of chromosomal breakage (Ahmad and Hanaoka, 2010).…”

A New Methodology for Diagnosis of Fanconi Anemia Based on Biological Dosimetry

“…4 On the other hand, ionizing radiation (IR) is a DNA-damaging physical agent, and studies have been evaluating the effects of IR on peripheral blood lymphocytes of Fanconipositive patients, with results either inconclusive or needing further improvements. [5][6][7][8][9] The process of irradiation directly influences the types and frequencies of chromosomal aberrations (CA), such as the type of irradiation source, dose, and dose-rates. Thus, the comparison of those researches is not straightforward since they generally employ different irradiation strategies.…”