Effects of mucus thickness and goblet cell hyperplasia on microdosimetric quantities characterizing the bronchial epithelium upon radon exposure

Abstract

Purpose: The most exposed tissue upon radon exposure is the bronchial epithelium where goblet cells serve as responsive and adaptable front-line defenders. They can rapidly produce a vast amount of mucus, and can change in number, in response to airway insults. The objective of the present study is to quantify the effects of mucus discharge and goblet cell hyperplasia on the microscopic dose consequences of macroscopic radon exposures. Methods: For this purpose, computational models of the bronchial epithelium and alpha-particle transport have been prepared and applied to quantify the hits received and doses absorbed by cell nuclei in case of different mucus thicknesses and goblet cell number. Results and conclusions: Both mucus discharge and induction of goblet cell hyperplasia reduce radiation burden at the cellular level, and as such they both can be considered as radioadaptive responses to radon exposure. As compared to basal cell hyperplasia, goblet cell hyperplasia is more effective in reducing the microscopic dose consequences of a given macroscopic exposure. Such changes in exposure geometry highlight the need for improvements in the application of biokinetic and dosimetry models for incorporated radionuclides as well as the dose and dose rate effectiveness factor.

Radon induced hyperplasia may provide an explanation for inverse exposure rate effect

“…Results show that average tissue dose, average hit number and dose of basal cells decrease by the increase of the measure of both basal and goblet cell hyperplasia [9,10]. Hit and dose distributions reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-particles in particular in case of goblet cell hyperplasia where both mucus thickening and the additional number of goblet cells decrease cellular burdens.…”

Internal microdosimetry of alpha-emitting radionuclides

“…The conjecture that hyperplasia occurs in the highly exposed carinal regions of the bronchial airways is supported by experimental (Rogers 2003) and histological findings (Auerbach et al 1961). Simulations indicated that an increase in progenitor cell number reduces not only the cell division rate for a given exposure rate, but also the microscopic energy deposition in the tissue (Madas 2016;Madas and Drozsdik 2018). As the number of progenitor cells increases, the bronchial epithelium tissue becomes thicker, thereby increasing the average distance between alpha decay sites and progenitor cells, and hence reducing the mean number of cellular hits.…”

“…While the increase of the cell division rate and the induction of DNA damage exhibit a synergistic response, results indicated that radon progeny alpha particles primarily cause mutations in the epithelium via the induced replacement of killed cells . Madas (2016), Madas and Drozsdik (2018), and Drozsdik and Madas (2019) also explored the role of hyperplasia on radon-induced lung cancer risk. The conjecture that hyperplasia occurs in the highly exposed carinal regions of the bronchial airways is supported by experimental (Rogers 2003) and histological findings (Auerbach et al 1961).…”

Effects of spatial variation in dose delivery: what can we learn from radon-related lung cancer studies?

“…One of the mechanisms reducing the cell division rate is the increase of progenitor cell number, as less divisions are required if there is a larger pool of cells capable of division. Based on histological (Auerbach et al 1961 ) and experimental evidence (McDowell et al 1979 ) as well as considerations in mathematical biology (Lander et al 2009 ), it was proposed that chronically high exposure to radon progeny can induce basal and goblet cell hyperplasia in the deposition hot spots (Madas and Balásházy 2011 ; Madas 2016b ; Madas and Drozsdik 2018 ).…”