Abstract
Results from previous studies suggest that alcohol consumption can be genotoxic on peripheral lymphocytes. The aim of our study was to examine the association of alcohol consumption and its genotoxic effect on hematopoietic stem cells in vivo. We investigated 156 healthy Japanese males in a cross-sectional study. Lifestyles, including alcohol drinking behavior and cigarette smoking status, were investigated by means of a self-completed questionnaire. Polymorphisms of ADH1B and ALDH2 were identified by PCR-restriction fragment length polymorphism (RFLP) analysis. The presence of micronuclei in transferrin-positive reticulocytes (MN-RET) was detected with a single-laser flow cytometer. Associations between the genetic polymorphisms, lifestyle factors, and MN-RET frequency were statistically analyzed. We found a significant difference in the mean frequencies of MN-RET between habitual drinkers and non-habitual drinkers (P=0.043), and between the ALDH2*1/*1 and ALDH2*2/*2 genotype (P=0.015). The ADH1B*2 and ALDH2*2 haplotype was estimated to have a significantly higher influence on MN-RET frequency than the ADH1B*2 and ALDH2*1 haplotype (P=0.00035), and the frequency of alcohol consumption played a significant role in MN-RET frequency on the background of the ADH1B*2 and ALDH2*1 haplotype (P=0.012). The results of our study suggest a possible association between the ADH1B and ALDH2 polymorphism and the genotoxic effects of alcohol drinking on hematopoietic stem cells.
Highlights
Chromosome alterations, such as chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN), which are directly visible as changes in chromosome structure, have been used as biomarkers for studying individuals exposed to known or potential genetic agents [1]
We found a significant difference in the mean frequencies of micronuclei in transferrin-positive reticulocytes (MN-RET) between habitual drinkers and non-habitual drinkers (P = 0.043), and between the aldehyde dehydrogenase-2 (ALDH2)*1/*1 and ALDH2*2/*2 genotype (P = 0.015)
The results of our study suggest a possible association between the ADH1B and ALDH2 polymorphism and the genotoxic effects of alcohol drinking on hematopoietic stem cells
Summary
Chromosome alterations, such as chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronuclei (MN), which are directly visible as changes in chromosome structure, have been used as biomarkers for studying individuals exposed to known or potential genetic agents [1]. The frequency of MN can be measured in human reticulocytes as a means to evaluate cytogenetic damage to hematopoietic stem cells resulting from chemo- or radiotherapy or unhealthy lifestyle factors [3,4,5] To date, these human reticulocyte studies have primarily used bone marrow aspirate or peripheral blood from splenectomized subjects (because human spleen can remove reticulocytes from the blood stream in 1 day, leaving only about 1% in the red blood cells). Abramsson-Zetterberg et al [6]
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