Expression of receptor for advanced glycation end products during rat tongue carcinogenesis by 4-nitroquinoline 1-oxide and effect of a selective cyclooxygenase-2 inhibitor, etodolac.
OBJECTIVE
The expression of a receptor for advanced glycation end products (RAGE) in lesions developed during rat tongue carcinogenesis by 4-nitroquinoline 1-oxide (4-NQO) and the effect of a selective cyclooxygenase-2 inhibitor, etodolac, were investigated.


METHODS
The tongue lesions were induced in Fischer 344 rats given 20-30 ppm 4-NQO in their drinking water for 12 weeks and then fed the basal diet containing 150 and 300 ppm of etodolac for 16 weeks, respectively.


RESULTS
The incidence of carcinomas in the 4-NQO-alone group was 100%. Etodolac significantly reduced the incidences of carcinomas to 66.7% (p < 0.05) and 50% (p < 0.01) at doses of 150 and 300 ppm, respectively. RAGE protein was immunohistochemically expressed in dysplastic cells and cancer cells of dysplasias and carcinomas. Etodolac significantly decreased the stainability of RAGE protein in dysplasias (p < 0.02) and carcinomas (p < 0.01). The expression of RAGE mRNA analyzed by RT-PCR was clearly detected in carcinomas developing in the 4-NQO-alone group. In carcinomas developing in the etodolac-treated group, RAGE mRNA expression significantly decreased (p < 0.03).


CONCLUSIONS
These results indicate that RAGE is involved in rat tongue carcinogenesis by 4-NQO and suggest that the chemopreventive effect exerted by etodolac is partly related to the inhibition of RAGE expression.
Yamamoto
Kazuhiko
K
Department of Oral and Maxillofacial Surgery, Nara Medical University, Nara, Japan. kazuyama@naramed-u.ac.jp
Kitayama
Wakashi
W
Denda
Ayumi
A
Sasahira
Tomonori
T
Kuniyasu
Hiroki
H
Kirita
Tadaaki
T
D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000473:pathology; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D017308:Etodolac / Q000494:pharmacology* / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D015363:Quinolones; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014059:Tongue / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D014062:Tongue Neoplasms / Q000139:chemically induced / Q000737:chemistry / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
C120195:4-nitroquinolone-1-oxide; D016588:Anticarcinogenic Agents; D052246:Cyclooxygenase 2 Inhibitors; D015363:Quinolones; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D017308:Etodolac; D015112:4-Nitroquinoline-1-oxide