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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 6  |  Page : 1285-1290

Chemopreventive potential of vanillic acid against 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis


1 Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamil Nadu, India
2 Department of Biochemistry, Government Arts College for Women, Krishnagiri, Tamil Nadu, India

Date of Web Publication28-Nov-2018

Correspondence Address:
Raju Kowsalya
Department of Biochemistry, Government Arts College for Women, Krishnagiri - 635 001, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.191057

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 > Abstract 


Objectives: The aim of this study was to evaluate the chemopreventive potential of vanillic acid against 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch oral carcinogenesis.
Materials and Methods: Determine the tumor incidence, tumor volume and burden, assessment of the status of Phase I and Phase II detoxification enzymes were measured in the liver and buccal mucosa of hamsters using specific colorimetric methods.
Results: One hundred percent tumor formation was observed in DMBA alone treated hamsters. Phase I and Phase II detoxification enzymes status were significantly altered DMBA-induced oral carcinogenesis. Vanillic acid (200 mg/kg bw p.o) significantly restored the biochemical variables of liver and buccal mucosa in DMBA + vanillic acid treated hamsters to near normal range compared with DMBA alone treated hamsters.
Conclusion: The present study thus shows chemopreventive potential of vanillic acid in DMBA-induced hamster buccal pouch carcinogenesis. Vanillic acid improves the phase I and phase II detoxification enzymes in DMBA treated hamsters.

Keywords: Vanillic acid, chemoprevention, 7,12-dimethylbenz(a)anthracene, detoxification


How to cite this article:
Vinoth A, Kowsalya R. Chemopreventive potential of vanillic acid against 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. J Can Res Ther 2018;14:1285-90

How to cite this URL:
Vinoth A, Kowsalya R. Chemopreventive potential of vanillic acid against 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. J Can Res Ther [serial online] 2018 [cited 2020 Jun 1];14:1285-90. Available from: http://www.cancerjournal.net/text.asp?2018/14/6/1285/191057




 > Introduction Top


Oral cancer is one of the common neoplasms worldwide and it is a common malignancy in developing countries particularly India.[1] Oral cancer accounts for 30–40% out of all cancer.[2] Oral cancer incidence in India is high and four times folded than other countryside.[3] Tobacco and alcohol consumption is main promoters/initiators of oral cancer in India.[4] Ninety percent of oral cancer is oral squamous cell carcinoma, histologically proved.[5]

Oral cancer is the eight rank of all cancer types worldwide[6] and in the region of the USA in its rate approximately 2.5% all cancer.[7] In the last three decades, 10-year survival rate is 51% and represents the survival rate could not be changed in over 30 years.[7] Late diagnosis and knowledge deficiency about oral cancer risks and symptoms of oral cancer, it attributed the low oral cancer survival rate. Secondary primary tumors may repetition 5–8 years of 22–42% oral cancer patients.[8]

Squamous cell carcinoma of the buccal mucosa is a tremendous candidate cancer for measurement of chemoprevention, oral administration of chemopreventive agents, results can be seen during experimental period, and alteration or suppression of genes or gene products participated in oral malignancies represents molecular targets oppose which chemopreventive method can be examined and confirmed. Syrian golden hamsters used as an oral cancer experimental model since 1954[9] and instead of more studies on prevention of oral squamous cell carcinoma by several chemopreventive entities. The previous studies reported that the Golden Syrian hamster model has been developing oral cancer, these tumors determined and characterize few of the genetic modifications appearing in premature and mature development of oral squamous cell carcinoma.[10] Several morphological and physiological characteristics those are observed in human oral squamous tumors are too observed in chemically induced hamster buccal pouch tumors. Hamster buccal pouch tumors and human oral squamous cell carcinoma tumors are both histologically and molecularly have the similarity and that may help as feasible biomarkers. Chemically induced hamster buccal pouch tumors are shown genetic events that are very similar to human oral malignancy.[11]

Chemoprevention is a novel, possible, and remarkable path to elucidate the anticancer effects of natural and synthetic compounds. Profound articles evidently proved chemopreventive agents that inhibit or down regulate the tumor formation and progression through biochemically and molecular level.[12]

The liver is the first-string for the change of integrity of xenobiotics, plays an important role in the alteration of the carcinogenic process. Determination of xenobiotic biotransformation enzymes such as cytochrome P450, cytochrome b5, glutathione-S-transferase (GST), glutathione reductase (GR), and reduced glutathione (GSH) in liver and buccal mucosa give the help to understand between the chemoprevention and chemopreventive entities potentials.[13],[14]

Vanillic acid is an oxidized form of vanillin and used as a flavoring agent, vanillic acid shows high free radical scavenging property compares to the vanillin.[15] Vanillic acid highly present in the roots of Angelica sinensis, it could be used in Traditional Chinese Medicine.[16] Stanely Mainzen Prince et al.,[17] reported that protective effect of vanillic acid and its free radical scavenging, antioxidant, and anti-inflammatory activities in isoproterenol-induced cardiotoxic rats. The present study deals to evaluate the chemopreventive potentials of vanillic acid against 7,12-dimethylbenz(a)anthracene (DMBA) stimulated oral cancer in the buccal pouch of the Golden Syrian hamster.


 > Materials and Methods Top


Chemicals and reagents

DMBA and vanillic acid was procured from Sigma-Aldrich Chemicals Pvt. Ltd., Bengaluru, Karnataka, India. All other chemicals used were of analytical grade obtained from HiMedia Laboratories, Bengaluru, Karnataka, India.

Animals

Twenty-four male Golden Syrian hamsters (8-week-old and 80–120g weighing) were procured from National Institute of Nutrition, Telangana, India. Experimental animals are maintained in the Central Animal House, RMMC and H, Annamalai University, Annamalainagar, Tamil Nadu, India. Experimental animals are housed in polypropylene cages and supplemented with standard pellet diet and water ad libitum. Animals were kept in a controlled environment with a 12 h light and 12 h dark cycle.

Experimental design

A total number of 24 experimental hamsters divided into four groups of six hamsters in each group. Group I hamsters as control and liquid paraffin only applied in their left buccal pouch of hamsters in the whole experimental period. Group II and III hamsters were painted with 0.5% DMBA in liquid paraffin thrice times a week for 14 weeks on their left buccal pouches of hamsters. No other treatment is given to the Group II hamsters. Vanillic acid at a dose of 200 mg/kg bw was orally administrated to Group III hamsters. Group IV hamsters treated with vanillic acid (200 mg/kg bw) alone all over the experimental session. The experiment was completed at the end of the 16th week all the animals were sacrificed by cervical dislocation. Biochemical estimations were performed in the liver and buccal mucosa of control and experimental hamsters. For histopathological examinations, buccal mucosa tissues were kept in 10% formalin and continuously developed and embedded with paraffin, serial 2–3 μm sections were cut in rotary microtome and stained with hematoxylin and eosin.

Induction of oral squamous cell carcinogenesis

0.5% DMBA was painted in the buccal pouches of Group II and Group III hamsters, three times a week for 14 weeks. Total tumors were estimated by macroscopically and tumor incidence was analyzed using Vernier caliper.

Biochemical estimations

Determine the Phase I and Phase II detoxification enzymes. End of the experimental session, hamsters was sacrificed, liver, and buccal mucosa tissue samples are rinsed with ice-cold saline and samples were homogenized then used for biochemical assessment. Cytochrome P450 and cytochrome b5, were assayed in liver and buccal mucosa according to the methods of Omura and Sato,[18] respectively. Status of GST in the buccal mucosa was determined by Habig et al.[19] GR activity was assayed using the method employed by Carlberg and Mannervik.[20] Reduced GSH in the liver and buccal mucosa activity was assayed by the method of Beutler and Kelly.[21] The activity of DT-diaphorase in the liver was estimated by Ernster.[22] The level of oxidized glutathione (GSSG) level in the buccal mucosa was described by the method of Tietze.[23]

Statistical analysis and software details

All data are expressed as mean ± standard deviation (n = 6). One-way analysis of variance followed by Duncan's multiple range test (DMRT) was employed to determine the statistical difference among experimental groups. The P < 0.05 among experimental groups results regarded as statistically significant.


 > Results Top


Incidence of oral neoplasm

Tumor incidence of hamsters was shown in [Table 1] and [Figure 1]. We found 100% tumor incidence in DMBA alone treated hamsters and it is confirmed by histopathologically as well-differentiated squamous cell carcinoma. Using of Vernier caliper to measure the tumor incidence in the diameter of each tumor. We observed no tumor formation in vanillic acid administrated and DMBA painted hamsters (Group III). Vanillic acid (200 mg/kg bw) prevents the tumor formation and decrease the risk rate of oral squamous cell carcinoma development.
Table 1: Incidence of oral neoplasm and histopathological changes in the buccal pouch of hamsters in the control and experimental groups (n=6)

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Figure 1: Gross appearance of buccal mucosa in control and experimental hamsters in each group. (a and d) Control and vanillic acid alone: Normal buccal pouch. (b) 7,12-dimethylbenz(a)anthracene alone: Well differentiated squamous cell carcinoma. (c) 7,12-dimethylbenz(a)anthracene + vanillic acid: Precancerous oral epithelial layers

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Histopathology evaluation

The histopathological features observed in the buccal mucosa of the control and treated animals in each group are shown in [Figure 2]. Control (Group I) and vanillic acid alone (Group IV) treated hamsters buccal mucosa hematoxylin and eosin (H and E) stained sections shows normal epithelium. No dysplastic change in the deeper stroma is unremarkable. DMBA alone (Group II) treated hamsters buccal mucosa H and E sections shows squamous epithelium with acanthosis, hyperkeratosis, and dysplastic changes with dyskeratosis (keratin pearl formation) and infiltration into deeper tissue and well differentiated squamous cell carcinoma. H and E stained sections of DMBA and vanillic acid-treated (Group III) hamsters shows mild dysplastic changes.
Figure 2: Hematoxylin and Eosin-stained sections of hamster buccal pouch 14 weeks after commencement of 7,12-dimethylbenz(a)anthracene treatment. (a and d) Control and vanillic acid alone: Normal epithelium, (b) 7,12-dimethylbenz(a)anthracene alone: Well differentiated squamous cell carcinoma, (c) 7,12-dimethylbenz(a)anthracene + vanillic acid: Mild dysplasia

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Levels of liver Phase I and Phase II detoxification agents

The levels of liver Phase I parameters (cytochrome P450 and cytochrome b5) and Phase II parameters (GSH, GR, and DT-diaphorase) was given in [Figure 3]. Vanillic acid alone (Group IV) treated hamsters did not show any significant variation as compared to control groups. DMBA alone (Group II) treated hamsters showed significantly increased Phase I detoxification enzymes while decreased Phase II detoxification enzymes in the liver. DMBA painted and vanillic acid administrated (Group III) hamsters reverts the levels of Phase I and Phase II detoxification enzymes into nigh to normal level in the liver.
Figure 3: Status of Phase I and Phase II detoxification agents in the liver of control and experimental animals in each group (n = 6). Values are expressed as mean ± Standard deviation values that do not share a common superscript between two groups differ significantly at P < 0.05 (Duncan's multiple range test). X – micromoles of cytochrome P450; Y – micromoles of cytochrome b5; C – micromoles of 2, 6-dichlorophenol reduced/min. GR = Glutathione reductase, GSH = Glutathione

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Levels of buccal mucosa Phase I and Phase II detoxification agents

The levels of liver Phase I parameters (cytochrome P450 and cytochrome b5) and Phase II parameters (GST, GSSG, and GSH) were given in [Figure 4]. Cytochrome P450, cytochrome b5, GST, and GSH were significantly increased meanwhile GSSG levels were lower levels in the DMBA alone treated hamsters (Group II) as compared to control hamsters. DMBA painted and vanillic acid administrated (Group III) hamsters reverts the levels of GSH, GST, and GSSG into near normal level. Vanillic acid alone treated animals (Group IV) no variance in the levels of GSH, GST, and GSSG as compared to control group hamsters (Group I).
Figure 4: Status of Phase I and Phase II detoxification agents in the buccal mucosa of control and experimental animals in each group (n = 6). Values are expressed as mean ± standard deviation values that do not share a common superscript between two groups different significantly at P < 0.05 (Duncan's multiple range test). X – micromoles of cytochrome P450; Y – micromoles of cytochrome b5; A – micromoles of 1-chloro 2, 4 dinitrobenzene/reduced glutathione conjugate formed/min. GSSG = Oxidized glutathione, GSH = Glutathione, GST = Glutathione-S-transferase

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 > Discussion Top


Worldwide oral cancer is the common and eight most cancer.[6] Oral carcinogenesis is a multifactorial disease, antecedent by different premalignant lesions.[24] Hamster buccal mucosa precancerous and cancerous lesions are closely mimics to the human oral cancer.[25] DMBA a site specific carcinogen frequently used as a carcinogen to develop tumors in the buccal pouches of Golden Syrian hamsters. Profound studies clearly revealed that DMBA-induced oral carcinogenesis be similar to human oral cancer.[26] We found 100% tumor level in DMBA alone treated hamsters in the end of the experimental session. We observed tumor incidence, tumor volume, and tumor burden in experimental hamsters. Severe hyperplasia, hyperkeratosis, and dysplasia were determined in the DMBA alone treated hamsters. DMBA and vanillic acid treated hamsters revealed severe hyperkeratosis, hyperplasia, and mild dysplasia. Results of this study proposed that vanillic acid suppresses tumor formation through DMBA-induced experimental oral carcinogenesis.

Overall survival rate of oral cancer is not considerably changed over the past three decades, because in spite of finding and treatment.[27] In consequence of, primary prevention by surcease of tobacco and alcohol consumption, in the company of dietary supplement/chemoprevention is of essential importance. In addition, this disease given a chance for secondary prevention, described as hindrance of recurrent, or new secondary primary oral malignant tumors. Certainly, 20% oral squamous cell carcinoma patients will show reappearance in 18 months postsurgery and 22–44% of patients will exhibit with secondary primary tumors within 5–8 years.[28]

Previous studies reported that number of chemopreventive entities prevents progression of tumors in the hamster buccal pouch carcinogenesis as induced earlier, during, or later by DMBA.[29] Chemopreventive agents have different mechanisms including detoxification metabolites, induction of Phase II enzymes, free radical scavenging, control of proliferation, inhibition of angiogenesis, upregulation of apoptotic markers, and suppression of DNA adduct formation.[29],[30]

Natural and synthetic compounds peculiarly efficiently chemoprevention of hamster buccal pouch carcinogenesis. DMBA induced tumors in hamsters, thus tumors was suppressed or inhibited or controlled by several agents such as green tea polyphenols,[31] retinyl acetate,[32] Ocimum sanctum,[33] 18-β-glycyrrhetinic acid,[34] lupeol,[35] cromolyn,[36] piperine,[37] apigenin[38] and different synthetic compounds. Our results are lend credence to these results.

The histopathological study of buccal pouches shows the establishment of well-differentiated squamous cell carcinoma, in hamsters treated with DMBA only. OSCC was detected by precancerous lesions such as hyperplasia and dysplasia and keratosis (56–70 days). Vanillic acid and DMBA treated hamsters unveiled that the vanillic acid is very effectually decrease the number of early lesions, as induced earlier, during, or later by DMBA treatment. Multiplicity of dysplasia was decreased to near normal levels and tumor formation was not seen in DMBA + vanillic acid administrated hamsters.

During cancer including oral cancer, carcinogens metabolically activated in the liver.[39] Activated metabolites are presented in the liver due to the upregulated performance of Phase I detoxification enzymes and lesser performance of Phase II detoxification enzymes.[40] We observed increased activity of Phase I detoxification enzymes and lesser activity of Phase II detoxification enzymes in the DMBA alone treated hamsters. Imbalance between the Phase I and Phase II enzymes may possibly result in malignant development.[41] Detoxification enzymes are regulated during the cells are exposed to carcinogens including DMBA.[42],[43] Our findings are lending credence to these results.


 > Conclusion Top


Vanillic acid at a dose of 200 mg/kg/bw improved the levels of Phase I and Phase II enzymes in the liver and buccal mucosa of hamsters treated with DMBA.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Anand R, Dhingra C, Prasad S, Menon I. Betel nut chewing and its deleterious effects on oral cavity. J Cancer Res Ther 2014;10:499-505.  Back to cited text no. 1
    
2.
Bose KS, Gokhale PV, Dwivedi S, Singh M. Quantitative evaluation and correlation of serum glycoconjugates: Protein bound hexoses, sialic acid and fucose in leukoplakia, oral sub mucous fibrosis and oral cancer. J Nat Sci Biol Med 2013;4:122-5.  Back to cited text no. 2
    
3.
Ganesan A, Kumar NG. Assessment of lipid peroxides in multiple biofluids of leukoplakia and oral squamous cell carcinoma patients-a clinico- biochemical study. J Clin Diagn Res 2014;8:ZC55-8.  Back to cited text no. 3
    
4.
Rao DN, Ganesh B, Rao RS, Desai PB. Risk assessment of tobacco, alcohol and diet in oral cancer – A case-control study. Int J Cancer 1994;58:469-73.  Back to cited text no. 4
    
5.
Epstein JB, Güneri P. The adjunctive role of toluidine blue in detection of oral premalignant and malignant lesions. Curr Opin Otolaryngol Head Neck Surg 2009;17:79-87.  Back to cited text no. 5
    
6.
Almadori G, Rigante M, Bussu F, Parrilla C, Gallus R, Barone Adesi L, et al. Impact of microvascular free flap reconstruction in oral cavity cancer: Our experience in 130 cases. Acta Otorhinolaryngol Ital 2015;35:386-93.  Back to cited text no. 6
    
7.
American Cancer Society. Cancer Facts & Figures 2013. Atlanta: American Cancer Society; 2013.  Back to cited text no. 7
    
8.
León X, Quer M, Diez S, Orús C, López-Pousa A, Burgués J. Second neoplasm in patients with head and neck cancer. Head Neck 1999;21:204-10.  Back to cited text no. 8
    
9.
Salley JJ. Histologic changes in the hamster cheek pouch during early hydrocarbon carcinogenesis. J Dent Res 1957;36:48-55.  Back to cited text no. 9
    
10.
Conti CJ. Animal models in the study of the premalignant process. Cancer Bull 1991;43:499-503.  Back to cited text no. 10
    
11.
Rajasekaran D, Kowsalya R, Selvasundaram R, Manoharan S. Enicostemma littorale protects cell surface abnormalities during DMBA-induced hamster buccal pouch carcinogenesis. Int J Pharm Bio Sci 2015;6:104-9.  Back to cited text no. 11
    
12.
Kathiresan S, Govindhan A. [6]-shogaol, a novel chemopreventor in 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. Phytother Res 2016;30:646-53.  Back to cited text no. 12
    
13.
Manson MM, Ball HW, Barrett MC, Clark HL, Judah DJ, Williamson G, et al. Mechanism of action of dietary chemoprotective agents in rat liver: Induction of phase I and II drug metabolizing enzymes and aflatoxin B1 metabolism. Carcinogenesis 1997;18:1729-38.  Back to cited text no. 13
    
14.
Sheweita SA. Drug-metabolizing enzymes: Mechanisms and functions. Curr Drug Metab 2000;1:107-32.  Back to cited text no. 14
    
15.
Tai A, Sawano T, Ito H. Antioxidative properties of vanillic acid esters in multiple antioxidant assays. Biosci Biotechnol Biochem 2012;76:314-8.  Back to cited text no. 15
    
16.
Duke JA. Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants. 999th ed. Boca Raton, FL, USA: CRC Press; 1992.  Back to cited text no. 16
    
17.
Stanely Mainzen Prince P, Rajakumar S, Dhanasekar K. Protective effects of vanillic acid on electrocardiogram, lipid peroxidation, antioxidants, proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats. Eur J Pharmacol 2011;668:233-40.  Back to cited text no. 17
    
18.
Omura T, Sato R. The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J Biol Chem 1964;239:2370-8.  Back to cited text no. 18
    
19.
Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130-9.  Back to cited text no. 19
    
20.
Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol 1985;113:484-90.  Back to cited text no. 20
    
21.
Beutler E, Kelly BM. The effect of sodium nitrite on red cell GSH. Experientia 1963;19:96-7.  Back to cited text no. 21
    
22.
Ernster L. DT-diaphorase. Methods Enzymol 1967;10:309-17.  Back to cited text no. 22
    
23.
Tietze F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Anal Biochem 1969;27:502-22.  Back to cited text no. 23
    
24.
Vargas-Ferreira F, Nedel F, Etges A, Gomes AP, Furuse C, Tarquinio SB. Etiologic factors associated with oral squamous cell carcinoma in non-smokers and non-alcoholic drinkers: A brief approach. Braz Dent J 2012;23:586-90.  Back to cited text no. 24
    
25.
Manoharan S, Rajasekaran D, Prabhakar MM, Karthikeyan S, Manimaran A. Modulating effect of Enicostemma littorale on the expression pattern of apoptotic, cell proliferative, inflammatory and angiogenic markers during 7,12-dimethylbenz (a)anthracene induced hamster buccal pouch carcinogenesis. Toxicol Int 2015;22:130-40.  Back to cited text no. 25
[PUBMED]  [Full text]  
26.
Manoharan S, Karthikeyan S, Essa MM, Manimaran A, Selvasundram R. An overview of oral carcinogenesis. Int J Nutr Pharmacol Neurol Dis 2016;6:51-62.  Back to cited text no. 26
  [Full text]  
27.
Casto BC, Knobloch TJ, Galioto RL, Yu Z, Accurso BT, Warner BM. Chemoprevention of oral cancer by lyophilized strawberries. Anticancer Res 2013;33:4757-66.  Back to cited text no. 27
    
28.
Iype EM, Pandey M, Mathew A, Thomas G, Nair MK. Squamous cell cancer of the buccal mucosa in young adults. Br J Oral Maxillofac Surg 2004;42:185-9.  Back to cited text no. 28
    
29.
Tanaka T. Chemoprevention of oral carcinogenesis. Eur J Cancer B Oral Oncol 1995;31B:3-15.  Back to cited text no. 29
    
30.
Chun KS, Kundu J, Chae IG, Kundu JK. Carnosol: A phenolic diterpene with cancer chemopreventive potential. J Cancer Prev 2014;19:103-10.  Back to cited text no. 30
    
31.
Li N, Han C, Chen J. Tea preparations protect against DMBA-induced oral carcinogenesis in hamsters. Nutr Cancer 1999;35:73-9.  Back to cited text no. 31
    
32.
Burge-Bottenbley A, Shklar G. Retardation of experimental oral cancer development by retinyl acetate. Nutr Cancer 1983;5:121-9.  Back to cited text no. 32
    
33.
Karthikeyan K, Ravichandran P, Govindasamy S. Chemopreventive effect of Ocimum sanctum on DMBA-induced hamster buccal pouch carcinogenesis. Oral Oncol 1999;35:112-9.  Back to cited text no. 33
    
34.
Kowsalya R, Vishwanathan P, Manoharan S. Chemopreventive potential of 18beta-glycyrrhetinic acid: An active constituent of liquorice, in 7,12-dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Pak J Biol Sci 2011;14:619-26.  Back to cited text no. 34
    
35.
Palanimuthu D, Baskaran N, Silvan S, Rajasekaran D, Manoharan S. Lupeol, a bioactive triterpene, prevents tumor formation during 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis. Pathol Oncol Res 2012;18:1029-37.  Back to cited text no. 35
    
36.
Karthikeyan S, Manoharan S. Tumor preventive potential of cromolyn in 7, 12- dimethylbenz(a)anthracene induced hamster buccal pouch carcinogenesis. Int J Pharm Bio Sci 2016;7:24-34.  Back to cited text no. 36
    
37.
Manoharan S, Balakrishnan S, Menon VP, Alias LM, Reena AR. Chemopreventive efficacy of curcumin and piperine during 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. Singapore Med J 2009;50:139-46.  Back to cited text no. 37
    
38.
Silvan S, Manoharan S. Apigenin prevents deregulation in the expression pattern of cell-proliferative, apoptotic, inflammatory and angiogenic markers during 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch carcinogenesis. Arch Oral Biol 2013;58:94-101.  Back to cited text no. 38
    
39.
Khambete N, Kumar R. Carcinogens and cancer preventors in diet. Int J Nutr Pharmacol Neurol Dis 2014;4:4-10.  Back to cited text no. 39
  [Full text]  
40.
Subapriya R, Velmurugan B, Nagini S. Modulation of xenobiotic-metabolizing enzymes by ethanolic neem leaf extract during hamster buccal pouch carcinogenesis. J Exp Clin Cancer Res 2005;24:223-30.  Back to cited text no. 40
    
41.
Wu X, Zhao H, Suk R, Christiani DC. Genetic susceptibility to tobacco-related cancer. Oncogene 2004;23:6500-23.  Back to cited text no. 41
    
42.
Wilkinson J 4th, Clapper ML. Detoxication enzymes and chemoprevention. Proc Soc Exp Biol Med 1997;216:192-200.  Back to cited text no. 42
    
43.
Acharya A, Das I, Chandhok D, Saha T. Redox regulation in cancer: A double-edged sword with therapeutic potential. Oxid Med Cell Longev 2010;3:23-34.  Back to cited text no. 43
    


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