Saving salivary glands from the collateral damage of radiation therapy
Seoul, Korea -- Researchers have shown that targeted overexpression of heat shock protein 25 prevents radiation-induced damage to salivary glands, a common consequence of treatment for head and neck cancer. The related report by Lee et al., "Radioprotective effect of HSP25 on submandibular glands of rats," appears in the November issue of The American Journal of Pathology.
Patients with head and neck cancer often receive radiation therapy as part of their treatment. However, the salivary glands, which frequently reside within the irradiation field, can become damaged at the same time. The resulting salivary dysfunction may involve dry mouth, oral infections, dental caries, and difficulty eating, some of which persist long after treatment ends, even permanently.
Dr. Yun-Sil Lee and colleagues examined whether salivary glands could be protected by heat shock proteins (HSPs), which are expressed by cells in an effort to counteract environmental stressors such as heat, hypoxia, and ionizing radiation. Using adenoviral vectors, the researchers specifically overexpressed HSP25 and HSP70i in submandibular salivary glands of rats. Rat salivary glands were then irradiated and monitored for radiation-induced changes.
In treated rats, HSP25 protected salivary gland function by maintaining gland weight, salivary flow rate, and salivary fluid composition, whereas HSP70i significantly protected only salivary flow rate. When specific damage to the glands was assessed, HSP25 and HSP70i both greatly diminished scarring, nuclear damage, and cell death (apoptosis), but HSP70i was slightly less effective. Finally, HSP25 and HSP70i preserved expression of aquaporin 5, which is important for water transport in salivary glands.
It is interesting to note that the results with HSP25 were similar to those observed with amifostine, an FDA-approved radioprotective drug. However, differences did exist: only amifostine protected all components of salivary fluid from change, but HSP25 afforded better protection from apoptosis than amifostine.
These results demonstrate the radioprotective effects of both heat shock proteins, with HSP25 providing the stronger defense. Thus, HSP25 delivery may represent a novel means of preventing the collateral damage associated with radiation therapy.
This work was supported by the Korea Science and Engineering Foundation (KOSEF) and Ministry of Science and Technology (MOST), Korean Government, through the National Nuclear Technology Program.
Work was directed by Dr. Yun-Sil Lee from the Korea Institute of Radiological and Medical Sciences, Seoul, Korea.
Lee H-J, Lee Y-J, Kwon H-C, Bae S, Kim S-H, Min J-J, Cho C-K, Lee Y-S. Radioprotective effect of HSP25 on submandibular glands of rats. Am J Pathol 2006 169:1601-1611
For press copies of the articles, please contact Dr. Audra Cox.
The American Journal of Pathology, the official journal of the American Society for Investigative Pathology (ASIP), seeks to publish high-quality original papers on the cellular and molecular mechanisms of disease. The editors accept manuscripts which report important findings on disease pathogenesis or basic biological mechanisms that relate to disease, without preference for a specific method of analysis. High priority is given to studies on human disease and relevant experimental models using cellular, molecular, biological, animal, chemical and immunological approaches in conjunction with morphology.
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