Of humans and hamsters: a comparative evaluation of carcinogen activation, DNA damage, cell proliferation, apoptosis, invasion, and angiogenesis in oral cancer patients and hamster buccal pouch carcinomas.
The hamster buccal pouch (HBP) carcinogenesis model is one of the most well characterized animal systems for analyzing the development of oral squamous cell carcinoma (OSCC), a common malignancy worldwide. HBP carcinomas that closely mimic human OSCC are useful in understanding the molecular mechanisms of neoplastic transformation. The present study is a comparative evaluation of markers of carcinogen activation, oxidative stress, cell proliferation, apoptosis, invasion, and angiogenesis in human and hamster OSCCs. Enhanced expression of CYP1A1 and CYP1B1 isoforms in both human and hamster oral tumours was associated with significantly increased expression of 8-hydroxy 2-deoxyguanosine (8-OHdG) indicating oxidative DNA damage. Analysis of markers of cell survival and proliferation revealed increased expression of PCNA, GST-P, and NF-kappaB with downregulation of p21, p53 and IkappaB in both human and hamster OSCCs. In addition, both human and hamster oral carcinomas displayed invasive, and angiogenic properties as revealed by dysregulated cytokeratin expression, downregulation of RECK, and increased expression of uPA, MMP-2 and-9, HIF-1alpha, and VEGF. The results reveal aberrant expression of multiple molecules in key signaling pathways in both human OSCCs and HBP carcinomas rendering the HBP model as an important tool for monitoring oral oncogenesis.
Nagini
Siddavaram
S
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamil Nadu, India. s_nagini@yahoo.com
Letchoumy
Paramasivame Vidjaya
PV
A
Thangavelu
T
Cr
Ramachandran
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000818:Animals; D017209:Apoptosis; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D049109:Cell Proliferation; D002610:Cheek / Q000473:pathology; D006224:Cricetinae; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007194:India; D008297:Male; D008647:Mesocricetus; D008875:Middle Aged; D023421:Models, Animal; D009062:Mouth Neoplasms / Q000378:metabolism*; D018384:Oxidative Stress
D014408:Biomarkers, Tumor; D000080242:8-Hydroxy-2'-Deoxyguanosine; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D003849:Deoxyguanosine