Mechanisms of Taste Bud Cell Loss after Head and Neck Irradiation

Abstract

Taste loss in human patients following radiotherapy for head and neck cancer is a common and significant problem, but the cellular mechanisms underlying this loss are not understood. Taste stimuli are transduced by receptor cells within taste buds, and like epidermal cells, taste cells are regularly replaced throughout adult life. This renewal relies on a progenitor cells adjacent to taste buds, which continually supply new cells to each bud. Here we treated adult mice with a single 8 Gy dose of X-ray irradiation to the head and neck, and analyzed taste epithelium at 1–21 days post-irradiation (dpi). We found irradiation targets the taste progenitor cells, which undergo cell cycle arrest (1–3 dpi) and apoptosis (within 1 dpi). Taste progenitors resume proliferation at 5–7 dpi, with the proportion of cells in S and M phase exceeding control levels at 5–6 and 6 dpi, respectively, suggesting that proliferation is accelerated and/or synchronized following radiation damage. Using BrdU birthdating to identify newborn cells, we found that the decreased proliferation following irradiation reduces the influx of cells at 1–2 dpi, while the robust proliferation detected at 6 dpi accelerates entry of new cells into taste buds. By contrast, the number of differentiated taste cells was not significantly reduced until 7 dpi. These data suggest a model where continued natural taste cell death, paired with temporary interruption of cell replacement underlies taste loss after irradiation.

Progress and renewal in gustation: new insights into taste bud development

“…The majority of K5/14 + cells appear to be transit amplifying cells, which divide frequently and are rapidly replaced; this interpretation is consistent with the demonstrated high proliferative index of lingual basal keratinocytes (Nguyen et al, 2012;Potten et al, 2002c). A smaller subset are stem cells, and lineage tracing results in sparsely distributed and long-lived epithelial clones ).…”

“…In mice, a single dose of radiation causes a transient interruption in the supply of new taste cells, resulting in a transient reduction in differentiated taste cells a few days later. Thus, these data provide a model for the response and recovery of the taste epithelium to a single radiation injury and, by extrapolation, for how taste function might be interrupted (Nguyen et al, 2012). However, these findings do not address how taste function is permanently altered by repeated head and neck irradiation in patients.…”

“…In rodents, taste function and buds are lost following radiation (Conger and Wells, 1969;Mossman et al, 1979;Yamazaki et al, 2009). Recent work has shown that, in mice, the impact of radiation is primarily on taste progenitor cells (Nguyen et al, 2012). Two days after irradiation, the proliferative index of taste progenitors is reduced by 80% and the flow of new cells into buds is halved.…”

Wnt/β-catenin signaling for dental regeneration

“…All three types of cells are thought to live for 10-14 days [38] and then undergo apoptosis [39]. This renewal relies on progenitor cells adjacent to taste buds, which continually supply new cells to each bud [40]. Taste loss in human patients following radiotherapy for head and neck cancer is a common and significant problem [41], which is caused by temporary interruption of cell replacement from progenitor cells paired with continued natural taste cell death [40].…”

“…This renewal relies on progenitor cells adjacent to taste buds, which continually supply new cells to each bud [40]. Taste loss in human patients following radiotherapy for head and neck cancer is a common and significant problem [41], which is caused by temporary interruption of cell replacement from progenitor cells paired with continued natural taste cell death [40]. to inhibit apoptosis respectively [53]; in addition, the ectopic Wnt activation in epithelium after radiation may also impair acini differentiation during tissue regeneration similarly as during embryonic branching morphogenesis [51].…”