The Effect of Desalivation on the Malignant Transformation of the Tongue Epithelium and Associated Stromal Myofibroblasts in a Rat 4-nitroquinoline 1-oxide-induced Carcinogenesis Model

Overview

Journal Int J Exp Pathol

Publisher Wiley

Specialty Pathology

Date 2010 Apr 1

PMID 20353426

Citations 2

Authors

Marilena Vered

Osnat Grinstein-Koren

Shoshana Reiter

Irit Allon

Dan Dayan

Affiliations

Soon will be listed here.

Abstract

The aim of our study was to analyse desalivated rat tongue epithelium for histopathological changes, proliferating cell nuclear antigen (PCNA), and epithelium-associated stromal myofibroblasts [SMF; alpha-smooth muscle actin (alphaSMA)] following 0.001% 4-nitroquinoline 1-oxide (4NQO) administration in drinking water. Results were compared with those of identically treated but salivated specimens. 4NQO was administered for 7, 14, 22 and 28 weeks. Tongue length was divided into anterior, middle and posterior 'thirds'. The histopathological changes per 'third' were scored as normal epithelium, hyperplasia, dysplasia, carcinoma-in-situ, and superficial and invasive carcinoma. The PCNA and alphaSMA stains were assessed by a point-counting method. At all time points, the histopathological changes in the anterior and middle thirds were higher in the desalivated than in the salivated group (P < 0.05) but almost identical in the posterior third (P > 0.05). PCNA scores were significantly lower in the desalivated vs. the salivated group at almost all time points and tongue thirds (P < 0.05). SMF were usually scarce in both groups, but there was a significant surge in the posterior third at 28 weeks: the score in the desalivated group was only about one-half that of the salivated group (P < 0.05). The absence of saliva seems to promote malignant transformation of the tongue epithelium in the early stages. PCNA cannot be regarded as a marker of proliferation and probably contributes to this process by other mechanisms. Emergence of SMF seems to be highly dependent on growth factors from saliva in addition to factors from cancerous cells.

Citing Articles

Exploring animal models in oral cancer research and clinical intervention: A critical review.

Khayatan D, Hussain A, Tebyaniyan H Vet Med Sci. 2023; 9(4):1833-1847.

PMID: 37196179 PMC: 10357283. DOI: 10.1002/vms3.1161.

Transcriptomic responses in the oral cavity of F344 rats and B6C3F1 mice following exposure to Cr(VI): Implications for risk assessment.

Thompson C, Rager J, Suh M, Ring C, Proctor D, Haws L Environ Mol Mutagen. 2016; 57(9):706-716.

PMID: 27859739 PMC: 5215477. DOI: 10.1002/em.22064.

References

Roos G, Landberg G, Huff J, Houghten R, Takasaki Y, Tan E . Analysis of the epitopes of proliferating cell nuclear antigen recognized by monoclonal antibodies. Lab Invest. 1993; 68(2):204-10. View

Mathison R, Davison J, Befus A . Neuroendocrine regulation of inflammation and tissue repair by submandibular gland factors. Immunol Today. 1994; 15(11):527-32. DOI: 10.1016/0167-5699(94)90209-7. View

Silva R, Ribeiro D, Salvadori D, Marques M . Placental glutathione S-transferase correlates with cellular proliferation during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide. Exp Toxicol Pathol. 2007; 59(1):61-8. DOI: 10.1016/j.etp.2007.02.010. View

Bodner L, Dayan D, Oberman M, Hirshberg A, Tal H . Healing of experimental wounds in sialadenectomized rat. J Clin Periodontol. 1992; 19(5):345-7. DOI: 10.1111/j.1600-051x.1992.tb00657.x. View

Ribeiro D, Salvadori D, Marques M . Abnormal expression of bcl-2 and bax in rat tongue mucosa during the development of squamous cell carcinoma induced by 4-nitroquinoline 1-oxide. Int J Exp Pathol. 2005; 86(6):375-81. PMC: 2517447. DOI: 10.1111/j.0959-9673.2005.00444.x. View

Dayan D, Bodner L, Horowitz I . Effect of salivary gland hypofunction on the healing of extraction wounds: a histomorphometric study in rats. J Oral Maxillofac Surg. 1992; 50(4):354-8. DOI: 10.1016/0278-2391(92)90397-i. View

Brown S, Niimi A, Lehmann A . Ubiquitination and deubiquitination of PCNA in response to stalling of the replication fork. Cell Cycle. 2009; 8(5):689-92. DOI: 10.4161/cc.8.5.7707. View

Ribeiro D, Kitakawa D, Domingues M, Cabral L, Marques M, Salvadori D . Survivin and inducible nitric oxide synthase production during 4NQO-induced rat tongue carcinogenesis: a possible relationship. Exp Mol Pathol. 2007; 83(1):131-7. DOI: 10.1016/j.yexmp.2007.02.006. View

Nakabayashi T, Sakata K, Sakata A, Kong L, Lau C, Letterio J . TGF-beta1 null mutation leads to CD154 upregulated expression in affected tissues. Inflammation. 2001; 25(2):69-73. DOI: 10.1023/a:1007158219974. View

10.

Vered M, Yarom N, Dayan D . 4NQO oral carcinogenesis: animal models, molecular markers and future expectations. Oral Oncol. 2005; 41(4):337-9. DOI: 10.1016/j.oraloncology.2004.07.005. View

11.

Kaplan I, ENGELBERG J, Dayan D . The effect of desalivation on 4-nitroquinoline-1-oxide-induced tongue carcinogenesis: a morphometric study of nucleolar organizer regions. J Oral Pathol Med. 2001; 30(1):48-52. DOI: 10.1034/j.1600-0714.2001.300108.x. View

12.

Stoimenov I, Helleday T . PCNA on the crossroad of cancer. Biochem Soc Trans. 2009; 37(Pt 3):605-13. DOI: 10.1042/BST0370605. View

13.

Dayan D, Hirshberg A, Kaplan I, Rotem N, Bodner L . Experimental tongue cancer in desalivated rats. Oral Oncol. 1997; 33(2):105-9. DOI: 10.1016/s0964-1955(96)00048-6. View

14.

Ohne M, Satoh T, Yamada S, Takai H . Experimental tongue carcinoma of rats induced by oral administration of 4-nitroquinoline 1-oxide (4NQO) in drinking water. Oral Surg Oral Med Oral Pathol. 1985; 59(6):600-7. DOI: 10.1016/0030-4220(85)90189-6. View

15.

Grundmann O, Mitchell G, Limesand K . Sensitivity of salivary glands to radiation: from animal models to therapies. J Dent Res. 2009; 88(10):894-903. PMC: 2882712. DOI: 10.1177/0022034509343143. View

16.

Narine K, de Wever O, Van Valckenborgh D, Francois K, Bracke M, DeSmet S . Growth factor modulation of fibroblast proliferation, differentiation, and invasion: implications for tissue valve engineering. Tissue Eng. 2007; 12(10):2707-16. DOI: 10.1089/ten.2006.12.2707. View

17.

Yousefzadeh G, Larijani B, Mohammadirad A, Heshmat R, Dehghan G, Rahimi R . Determination of oxidative stress status and concentration of TGF-beta 1 in the blood and saliva of osteoporotic subjects. Ann N Y Acad Sci. 2007; 1091:142-50. DOI: 10.1196/annals.1378.062. View

18.

Garg P, Burgers P . Ubiquitinated proliferating cell nuclear antigen activates translesion DNA polymerases eta and REV1. Proc Natl Acad Sci U S A. 2005; 102(51):18361-6. PMC: 1317920. DOI: 10.1073/pnas.0505949102. View

19.

Ribeiro D, Salvadori D, da Silva R, Ribeiro Darros B, Marques M . Genomic instability in non-neoplastic oral mucosa cells can predict risk during 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Oral Oncol. 2004; 40(9):910-5. DOI: 10.1016/j.oraloncology.2004.04.010. View

20.

Eyden B . The myofibroblast: a study of normal, reactive and neoplastic tissues, with an emphasis on ultrastructure. J Submicrosc Cytol Pathol. 2008; :7-166. View