Effects of keratinocyte growth factor in the squamous epithelium of the upper aerodigestive tract of normal and irradiated mice.
OBJECTIVE
To investigate the effects of keratinocyte growth factor (KGF) on the structure of the stratified squamous epithelium of the tongue, buccal mucosa and oesophagus of normal and irradiated mice.


METHODS
Female BDF1 mice were exposed to total body irradiation from a caesium source. The irradiated mice and normal, unirradiated mice were injected with 5 mg/kg per day KGF or vehicle. Thickness and proliferation in the epithelium were measured.


RESULTS
KGF caused epithelial thickening of the non-keratinized layers in oral epithelium in normal mice. It increased the number of nucleated layers and influenced differentiation of post-mitotic cells in the upper layers by increasing the size and number of keratohyalin granules, and the number of desmosomes. Single and fractionated doses of radiation caused inhibition of proliferation as detected by markedly reduced BrdU incorporation following exposure, followed by epithelial atrophy. KGF treatment of mice reversed the inhibition of proliferation and atrophy that occurred in control irradiated mice.


CONCLUSIONS
These data show that KGF reverses epithelial atrophy in mouse oral cavity caused by irradiation and suggest that KGF may be useful for the treatment of mucositis of the upper aerodigestive tract of patients treated with aggressive regimens of radiation therapy.
Farrell
C L
CL
Department of Pathology, Amgen Inc., Thousand Oaks, CA 91320-1789, USA. cfarrell@amgen.com
Rex
K L
KL
Kaufman
S A
SA
Dipalma
C R
CR
Chen
J N
JN
Scully
S
S
Lacey
D L
DL
D000818:Animals; D004947:Esophagus / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D005260:Female; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D006133:Growth Substances / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D012333:RNA, Messenger / Q000032:analysis; D014916:Whole-Body Irradiation
C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D006133:Growth Substances; D012333:RNA, Messenger; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors