Effects of in vivo treatments of nicotine and benzo[a]pyrene on the epidermal growth factor receptor in hamster buccal pouch.
This study was conducted to investigate the effects of two major ingredients in cigarette smoke, benzo-alpha-pyrene (BP) and nicotine (Nic), on epidermal growth factor (EGF) receptor in hamster buccal pouch. Adult male Syrian hamsters were treated by apically swabbing the buccal pouch with mineral oil (Control), 0.5 microgram/ml of BP, Nic or BP+Nic in mineral oil, twice a day, 5 days a week for 4 weeks. The BP+Nic treatment resulted in a significant reduction of submandibular gland (SG) EGF (Control vs. BP+Nic, 6.93 +/- 1.31 vs. 4.77 +/- 0.26* ng/g wet tissue, mean +/- S.D., n=5,*P < 0.05). Treatment with BP or Nic also caused a reduction, although not statistically significant, of EGF in SG extract. For the receptor study, all treatments significantly increased [125I]EGF binding to membrane preparations of buccal pouch as compared to Control (Control, BP, Nic, BP+Nic; 12.2 +/- 0.9, 20.5 +/- 2.2*, 17.0 +/- 1.3*, 21.2 +/= 1.6* fmol/mg prot. (mean +/- S.E.M.), n=5, P < 0.05). Scatchard analysis revealed that the higher EGF binding to the BP+Nic-treated sample was due to the higher number of receptors, but not higher affinity. Data from protein kinase study indicate that EGF stimulated phosphorylation of 170- and 150-kDa proteins in buccal membrane preparations. Treatment of BP+Nic resulted in reductions in EGF-stimulated phosphorylation of 170- and 150-kDa proteins by 19 and 72%, respectively. The present study has established an animal model which will benefit investigation of the mechanism by which tobacco alters the EGF receptor in oral buccal mucosa.
Wang
S L
SL
Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark 07103-2400, USA.
Feng
J
J
Correa
A
A
Brigham
M
M
Wu-Wang
C Y
CY
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D003367:Cotinine / Q000097:blood; D006224:Cricetinae; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D011485:Protein Binding / Q000187:drug effects; D013363:Submandibular Gland / Q000378:metabolism
D010750:Phosphoproteins; D001564:Benzo(a)pyrene; D004815:Epidermal Growth Factor; D009538:Nicotine; D066246:ErbB Receptors; D003367:Cotinine