Nanoscale intracellular mass-density alteration as a signature of the effect of alcohol on early carcinogenesis: A transmission electron microscopy (TEM) study

TL;DR

This study uses TEM imaging and nanoscale disorder analysis to investigate how alcohol influences early carcinogenic changes in colonic cells, revealing alcohol's role as an enhancer of nanoscale disorder in precancerous tissues.

Contribution

First to quantify alcohol's effect on early carcinogenic cellular nanoscale disorder using TEM and mesoscopic physics analysis.

Findings

Alcohol does not significantly alter nanoscale structure in normal cells.

Alcohol enhances nanoscale disorder in precancerous cells.

Nanoscale disorder correlates with early carcinogenesis stages.

Abstract

Alcohol consumption interferes with the functioning of multiple organ systems, causing changes in the chemistry, physiology and pathology of tissues and cellular organelles. Although epigenetic modifications underlie the development of cancer, exposure to carcinogenic chemicals, such as alcohol, can also contribute to disease development. However, the effects of chronic alcoholism on normal or pre-carcinogenic cells/tissues in different organelles are not well understood. Therefore, we herein study the effect of alcohol consumption on colonic nucleus using control and azoxymethane (AOM) and dextran sulfate sodium (DSS) treated carcinogenic mice. Previous studies showed that progression of carcinogenesis is associated with increase in the degree of intranuclear nanoscale structural disorder. In the present work, we quantify the degree of nanostructural disorder as a measure of carcinogenesis. To accomplish this, transmission electron microscopy (TEM) imaging of respective colonic epithelial cell nuclei are used to construct disordered optical lattices, and the properties of nanoscale disorder are then studied by analyzing the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices. Nanoscale structural disorder strength, as a marker of cancer progression, is measured in the length scale of 10 to 75 nm. Results show no significant visible effect in nanoscale structural changes on colon cell nuclei from alcohol exposure. However, alcohol was found to act as an enhancer of nanoscale disorder in precancerous cells and, hence, carcinogenic processes. To the best of our knowledge, this is the first study to quantify the effect of alcohol on early carcinogenic biological cells, using mesoscopic condensed matter physics.