8-hydroxy-2--deoxyguanosine and Mouth-Neoplasms

The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´-deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication.. We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of follow-up. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus.. Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001).. All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Carcinoma, Squamous Cell; Deoxyguanosine; DNA Damage; Free Radicals; Humans; Mouth Neoplasms; Oxidative Stress

Cryptocaryone (CPC) was previously reported as preferential for killing natural products in oral cancer cells. However, its radiosensitizing potential combined with ultraviolet C (UVC) cell killing of oral cancer cells remains unclear. This study evaluates the combined anti-proliferation effect and clarifies the mechanism of combined UVC/CPC effects on oral cancer cells. UVC/CPC shows higher anti-proliferation than individual and control treatments in a low cytotoxic environment on normal oral cells. Mechanistically, combined UVC/CPC generates high levels of reactive oxygen species and induces mitochondrial dysfunction by generating mitochondrial superoxide, increasing mitochondrial mass and causing the potential destruction of the mitochondrial membrane compared to individual treatments. Moreover, combined UVC/CPC causes higher G2/M arrest and triggers apoptosis, with greater evidence of cell cycle disturbance, annexin V, pancaspase, caspases 3/7 expression or activity in oral cancer cells than individual treatments. Western blotting further indicates that UVC/CPC induces overexpression for cleaved types of poly (ADP-ribose) polymerase and caspase 3 more than individual treatments. Additionally, UVC/CPC highly induces γH2AX and 8-hydroxy-2'-deoxyguanosine adducts as DNA damage in oral cancer cells. Taken together, CPC shows a radiosensitizing anti-proliferation effect on UVC irradiated oral cancer cells with combined effects through oxidative stress, apoptosis and DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Apoptosis; Cell Line, Tumor; Cell Proliferation; DNA Damage; G2 Phase Cell Cycle Checkpoints; Humans; Membrane Potential, Mitochondrial; Mouth Neoplasms; Poly(ADP-ribose) Polymerases; Pyrones; Reactive Oxygen Species; Ultraviolet Rays

To determine whether the breast cancer susceptibility gene 1 (BRCA1) regulates oxidative damage in oral cancer cells by interacting with nuclear factor erythroid 2-like 2 (NRF2).. The BRCA1 gene was silenced in CAL-27 and DOK cells using specific shRNA, and NRF2 was activated with sulforaphane. The expression levels of BRCA1, NRF2 and its target genes were assessed by quantitative real-time polymerase chain reaction and western blotting. Cell counting kit-8 assay was used to detect cell proliferation, apoptosis was detected by flow cytometry, and 8-OXo-2'-deoxyguanosine level was measured by enzyme-linked immunosorbent assay. The expression of BRCA1 and NRF2 in patients with oral leukoplakia and oral squamous cell carcinoma were evaluated by immunohistochemistry.. BRCA1 knockdown downregulated NRF2 and its target genes, increased proliferation rates, reduced apoptosis, and increased 8-OXo-2'-deoxyguanosine levels compared to the control. Activation of NRF2 by sulforaphane significantly upregulated NRF2 levels in the BRCA1-depleted cells, and restored proliferation, apoptosis and 8-OXo-2'-deoxyguanosine level in a dose-dependent manner. Compared with patients with leukoplakia, BRCA1 and NRF2 expression were increased in patients with oral squamous cell carcinoma.. BRCA1 depletion increases oxidative damage and promotes the malignant phenotype, which may eventually promote oral carcinogenesis. The NRF2-activator sulforaphane is a potential chemo-preventive agent for oral cancer.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Apoptosis; BRCA1 Protein; Female; Humans; Isothiocyanates; Mouth Neoplasms; NF-E2-Related Factor 2; Oxidative Stress; Squamous Cell Carcinoma of Head and Neck; Sulfoxides

Squamous Cell Carcinoma is almost always preceded by potentially malignant disorders in the oral cavity before malignant transformation. Characterization of  8-OHdG from the saliva offers a relatively non-invasive, simple and efficient methodology for monitoring oxidative stress in subjects of Premalignant oral disorders (PMOD) and Oral Squamous Cell Carcinoma (OSCC). Hence the aim of the current study is to estimate the levels of salivary 8-hydroxydeoxyguanosine (8-OHdG) as a potential DNA Damage Biomarker in OSMF and OSCC patients in comparison to healthy individuals to assess disease progression from potentially malignant oral disorder to frank malignancy.. The study was conducted among 90 patients [Oral Squamous cell carcinoma (n=30) and Oral Submucous Fibrosis (n=30) and healthy gender and age matched controls (n=30)]. 4ml of unstimulated saliva was collected from each of the subjects and was subjected to Sandwich ELISA for the quantification of salivary 8-OHdG. Statistical analysis was done using ANOVA, and p value was set at ≤0.05.. The mean age of OSCC patients were 56.8±11.8 years. Smoking was the most prevalent adverse habit among this group (66.6%) followed by Smokeless tobacco chewers (40%). The mean age of OSMF patients was 46.2± 9.8 years. Smokeless tobacco was the most predominant habit among the OSMF patients (83.33%) followed by smoking (33.33%). The mean OHdG levels among the controls was 6.59±1.47 (ng/dl) and almost doubled in patients of OSMF 13.89±1.96(ng/dL) and further raised in OSCC patients 19.96 ± 2.11 (ng/dL). These levels showed a highly significant difference (p <0.0001) in mean on comparison by using one-way ANOVA. Pearson correlation between the groups were also statistically significant (p=0.000).. There were significant differences in the concentration of salivary 8-OHdG between healthy controls, OSMF, and OSCC patients. Hence, 8-OHdG can be used as a novel biomarker of DNA damage to assess disease progression.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Cell Transformation, Neoplastic; Disease Progression; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mouth Neoplasms; Prognosis; Saliva

To investigate the effect of oxidative stress biomarkers on the risk of potentially malignant oral disorders (PMODs).. A total of 208 male adults with PMODs and an equal number of same-age control patients were enrolled. Plasma biomarkers of oxidative stress, measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane (8-ISO), were determined using enzyme-linked immunosorbent assay (ELISA) kits. PMODs were diagnosed in accordance with the World Health Organization (WHO) guidelines.. A significant association between a high level of 8-ISO and an increased risk of PMODs was identified [odds ratio (OR)=1.71, 95% confidence interval (CI)=1.12-2.63; p=0.013]. This positive association was stronger among patients with PMOD subtype of leukoplakia (OR=1.94, 95% Cl=1.24-3.06; p=0.004). However, no significant association was observed between plasma 8-OHdG levels and overall risk of PMODs or subtypes.. Increased plasma 8-ISO levels may indicate the prominence of lipid peroxidation in the development of PMODs, particularly leukoplakia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers; Deoxyguanosine; Dinoprost; Humans; Lipid Peroxidation; Male; Middle Aged; Mouth Neoplasms; Oxidative Stress; Precancerous Conditions; Risk Factors

Several functionalized chromones, the key components of naturally occurring oxygenated heterocycles, have anticancer effects but their sulfone compounds are rarely investigated. In this study, we installed a sulfonyl substituent to chromen-4-one skeleton and synthesized CHW09 to evaluate its antioral cancer effect in terms of cell viability, cell cycle, apoptosis, oxidative stress, and DNA damage. In cell viability assay, CHW09 preferentially kills two oral cancer cells (Ca9-22 and CAL 27), less affecting normal oral cells (HGF-1). Although CHW09 does not change the cell cycle distribution significantly, CHW09 induces apoptosis validated by flow cytometry for annexin V and by western blotting for cleaved poly(ADP-ribose) polymerase (PARP), and caspases 3/8/9. These apoptosis signaling expressions are partly decreased by apoptosis inhibitor (Z-VAD-FMK) or free radical scavenger (N-acetylcysteine). Furthermore, CHW09 induces oxidative stress validated by flow cytometry for the generations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), and the suppression of mitochondrial membrane potential (MMP). CHW09 also induces DNA damage validated by flow cytometry for the increases of DNA double strand break marker γH2AX and oxidative DNA damage marker 8-oxo-2'-deoxyguanosine (8-oxodG). Therefore, our newly synthesized CHW09 induces apoptosis, oxidative stress, and DNA damage, which may lead to preferential killing of oral cancer cells compared with normal oral cells.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Survival; Chromones; Deoxyguanosine; DNA Damage; Free Radical Scavengers; Humans; Membrane Potential, Mitochondrial; Mouth Neoplasms; Organ Specificity; Oxidation-Reduction; Oxidative Stress; Poly(ADP-ribose) Polymerases; Reactive Oxygen Species

Isobutyl-deoxynyboquinone (IB-DNQ) is a selective substrate for NAD(P)H:quinone oxidoreductase (NQO1), an enzyme overexpressed in many solid tumors. Following activation by NQO1, IB-DNQ participates in a catalytic futile reduction/reoxidation cycle with consequent toxic reactive oxygen species generation within the tumor microenvironment. To elucidate the potential of IB-DNQ to serve as a novel anticancer agent, in vitro studies coupled with in vivo pharmacokinetic and toxicologic investigations in the domestic felid species were conducted to investigate the tractability of IB-DNQ as a translationally applicable anticancer agent. First, using feline oral squamous cell carcinoma (OSCC) as a comparative cancer model, expressions of NQO1 were characterized in not only human, but also feline OSCC tissue microarrays. Second, IB-DNQ mediated cytotoxicity in three immortalized feline OSCC cell lines were studied under dose-dependent and sequential exposure conditions. Third, the feasibility of administering IB-DNQ at doses predicted to achieve cytotoxic plasma concentrations and biologically relevant durations of exposure were investigated through pharmacokinetic and tolerability studies in healthy research felines. Intravenous administration of IB-DNQ at 1.0-2.0 mg/kg achieved peak plasma concentrations and durations of exposure reaching or exceeding predicted in vitro cytotoxic concentrations. Clinical adverse side effects including ptyalism and tachypnea exhibited during and post-IV infusion of IB-DNQ were transient and tolerable. Additionally, IB-DNQ administration did not produce acute or delayed-onset unacceptable hematologic, non-hematologic, or off-target oxidative toxicities. Collectively, the findings reported here within provide important safety and pharmacokinetic data to support the continued development of IB-DNQ as a novel anticancer strategy for NQO1 expressing cancers.

Topics: 8-Hydroxy-2'-Deoxyguanosine; A549 Cells; Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cats; Cell Line, Tumor; Cell Survival; Deoxyguanosine; Female; HEK293 Cells; Humans; Mouth Neoplasms; NAD(P)H Dehydrogenase (Quinone); Quinones

The objectives of this study are to analyze oxidative DNA and lipid damage using salivary 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and vitamins C and E in oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, oral squamous cell carcinoma (SCC), and controls and to determine the value of salivary biomarkers in the diagnosis of oral pre-cancer and cancer patients.. Unstimulated saliva was collected from a group of patients diagnosed with 40 oral squamous cell carcinoma (OSCC), 40 oral lichen planus lesions, 40 oral leukoplakia, 40 oral submucous fibrosis, and from a control group of healthy age- and gender-matched individuals. Salivary 8-OHdG, MDA, and vitamins C and E were measured.. Squamous cell carcinoma and pre-cancer patients showed significantly higher levels of salivary 8-OHdG and MDA and lower levels of vitamins C and E when compared to levels in healthy normal subjects. The specificity and sensitivity of the combination of 8-OHdG, MDA, vitamin C, and vitamin E are high for the diagnosis of oral pre-cancer and SCC compared to an individual biomarker approach using either 8-OHdG, MDA, or vitamin C and vitamin E independently.. This study indicates the presence of oxidative DNA and lipid damage in pre-cancerous and SCC patients. It is postulated that the mechanism may have a significant link to carcinogenesis in oral cancer. Detection of salivary 8-OHdG, MDA, vitamin C, and vitamin E can act as suitable diagnostic biomarkers of oral pre-cancer and cancer.. Of clinical importance is that salivary 8-OHdG, MDA, vitamin C, and vitamin E could play a significant role in oral cancer and pre-cancer patients and could therefore be useful for diagnosis in patients with oral lichen planus lesions, oral leukoplakia, oral submucous fibrosis, and oral squamous cell carcinoma.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Ascorbic Acid; Biomarkers; Biopsy; Carcinoma, Squamous Cell; Case-Control Studies; Deoxyguanosine; Female; Free Radicals; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Precancerous Conditions; Risk Factors; Saliva; Sensitivity and Specificity; Vitamin E

Overexpression of peroxiredoxin 1 (Prx1) has been observed in numerous cancers including oral squamous cell carcinoma (OSCC). The precise molecular mechanism of up-regulation of Prx1 in carcinogenesis, however, is still poorly understood. The objective of this study is to investigate the relationship between Prx1 and hypoxia, and potential mechanism(s) of Prx1 in OSCC cell line SCC15 and xenograft model. We treated wild-type and Prx1 knockdown SCC15 cells with transient hypoxia followed by reoxygenation. We detected the condition of hypoxia, production of reactive oxygen species (ROS), and expression and/or activity of Prx1, heme oxygenase 1 (HO-1) and nuclear factor-kappa B (NF-κB). We found that hypoxia induces ROS accumulation, up-regulates Prx1, increases NF-κB translocation and DNA binding activity, and down-regulates HO-1 in vitro. In Prx1 knockdown cells, the expression level of HO-1 was increased, while NFκB translocation and DNA binding activity were decreased after hypoxia or hypoxia/reoxygenation treatment. Moreover, we mimicked the dynamic oxygenation tumor microenvironment in xenograft model and assessed the above indices in tumors with the maximal diameter of 2 mm, 5 mm, 10 mm or 15 mm, respectively. Our data showed that tumor hypoxic condition and expression of Prx1 are significantly associated with tumor growth. The expression of HO-1 and NF-κB, and NF-κB DNA binding activity were significantly elevated in 15 mm tumors, and the level of 8-hydroxydeoxyguanosine was increased in 10 mm and 15 mm tumors, compared to those in size of 2 mm. The results from this study provide experimental evidence that overexpression of Prx1 is associated with hypoxia, and Prx1/NF-κB/HO-1 signaling pathway may be involved in oral carcinogenesis.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Carcinogenesis; Carcinoma, Squamous Cell; Deoxyguanosine; Gene Expression Regulation, Neoplastic; Heme Oxygenase-1; Homeodomain Proteins; Humans; Hypoxia; Male; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms; Neoplasm Transplantation; NF-kappa B; Oxygen; Protein Transport; Reactive Oxygen Species; Signal Transduction; Tumor Burden; Tumor Microenvironment

The aim of this study was to evaluate oxidative stress status in the saliva of patients with oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC).. Thirty-two patients with OLP, 26 patients with OSCC, and 30 non-involved subjects were enrolled in this study. The study was conducted at the Cancer Department, Clinic of Oral Medicine, Tehran University of Medical Sciences. The unstimulated whole saliva malondialdehyde (MDA), as an indicator of lipid peroxidation, the total antioxidant capacity (TAC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were assayed by thiobarbituric acid, ferric reducing antioxidant potential (FRAP), and ELISA method, respectively. The TAC/MDA ratio was used as an index of oxidative stress status. Data were analyzed by ANOVA followed by the Tukey's post hoc test.. There were no significant differences in saliva TAC and MDA levels between OLP and control, and also between OLP and OSCC patients. MDA and 8-OHdG were significantly higher but TAC was lower in OSCC patients than control. TAC/MDA ratio was significantly lower in patients with OSCC than both OLP patients and control. TAC/MDA ratio was significantly lower but 8-OHdG was higher in patients with OLP compared to control. This suggests that patients with OLP and OSCC are more susceptible to an imbalance of antioxidant-oxidative stress status.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Carcinoma, Squamous Cell; Case-Control Studies; Deoxyguanosine; DNA Damage; Female; Free Radicals; Humans; Lichen Planus, Oral; Male; Malondialdehyde; Middle Aged; Mouth Mucosa; Mouth Neoplasms; Oxidative Stress; Precancerous Conditions; Predictive Value of Tests; Reference Values; Risk Assessment; Saliva; Salivary Proteins and Peptides; Statistics, Nonparametric

Extensive research within the past half-century has indicated that curcumin (diferuloylmethane), a yellow pigment in curry powder, exhibits anti-oxidant, anti-inflammatory, and pro-apoptotic activities. We investigated whether the anti-pre-cancer activities assigned to curcumin are mediated through an anti-oxidant and DNA-protecting mechanism. Patients with oral leukoplakia, oral submucous fibrosis or lichen planus, and healthy individuals (n = 25 for each group) aged 17-50 years were selected. Salivary and serum oxidative markers such as malonaldehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), vitamins C and E were measured just prior to the intake of curcumin, after one week of curcumin intake and following clinical cure of precancerous lesions. Serum and salivary vitamins C and E showed increases, while MDA and 8-OHdG levels showed decreases in patients with oral leukoplakia, submucous fibrosis and lichen planus after intake of curcumin for all categories of precancerous lesions. The changes in these values were observed to be statistically significant after clinical cure of the disease (P < 0.05). The five-point rating scale for pain, as well as lesion size in oral leukoplakia, submucous fibrosis and lichen planus, improved significantly (P < 0.05). In addition, in submucous fibrosis, mouth opening (P < 0.05) recovered significantly. In oral leukoplakia, submucous fibrosis and lichen planus, the levels of serum and salivary vitamins C and E increased significantly, while MDA and 8-OHdG levels decreased after 131(15), 211(17), and 191(18) days, respectively. Values for serum and salivary vitamins C and E showed a significant decrease in oral leukoplakia, submucous fibrosis and lichen planus, in contrast to healthy individuals, but increased significantly in all groups subsequent to curcumin administration after clinical cure of lesions. Based on these results, we can conclude that curcumin mediates its anti-pre-cancer activities by increasing levels of vitamins C and E, and preventing lipid peroxidation and DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Adult; Antioxidants; Ascorbic Acid; Biomarkers; Curcumin; Deoxyguanosine; DNA; DNA Damage; Female; Follow-Up Studies; Free Radical Scavengers; Humans; Leukoplakia, Oral; Lichen Planus, Oral; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Mouth Neoplasms; Oral Submucous Fibrosis; Oxidative Stress; Pain Measurement; Precancerous Conditions; Protective Agents; Saliva; Vitamin E; Young Adult

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.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Animals; Apoptosis; Aryl Hydrocarbon Hydroxylases; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cell Proliferation; Cheek; Cricetinae; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Deoxyguanosine; DNA Damage; Humans; India; Male; Mesocricetus; Middle Aged; Models, Animal; Mouth Neoplasms; Oxidative Stress

The objective of this study was to evaluate the chemopreventive potential of the black tea polyphenols Polyphenon-B and BTF-35 during the preinitiation phase of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Hamsters were divided into six groups. Animals in groups 2 and 3 received diet containing Polyphenon-B and BTF-35, respectively, 4 weeks before carcinogen administration when they were 6 weeks of age and continued until the final exposure to carcinogen. At 10 weeks of age, animals in groups 1, 2, and 3 were painted with 0.5% DMBA three times a week for 14 weeks. Animals in groups 4 and 5 were given Polyphenon-B and BTF-35 alone, respectively, as in groups 2 and 3. Animals in group 6 served as control. All the animals were sacrificed after an experimental period of 18 weeks. Phase I and phase II xenobiotic-metabolizing enzymes and 8-hydroxy-deoxyguanosine (8-OH-dG) in the buccal pouch and liver were used as biomarkers of chemoprevention. Hamsters painted with DMBA showed increased expression of 8-OH-dG and enhanced activities of phase I (CYP450; total as well as CYP1A1, 1A2, and 2B isoforms and cytochrome b5) and phase II (GST and quinone reductase) xenobiotic-metabolizing enzymes with increased immunohistochemical expression of CYP1A1, and CYP1B1 isoforms in the buccal pouch. This was accompanied by increased phase I and decreased phase II enzyme activities in the liver. Administration of Polyphenon-B and BTF-35 significantly decreased tumor incidence, oxidative DNA damage, phase I enzyme activities as well as expression of CYP1A1 and CYP1B1 isoforms, while enhancing phase II enzyme activities in the buccal pouch and liver. Our results provide a mechanistic basis for the chemopreventive potential of black tea polyphenols. Furthermore, the greater efficacy of BTF-35 in chemoprevention of HBP carcinomas via inhibition of oxidative DNA damage and modulation of xenobiotic-metabolizing enzymes may have a major impact in human oral cancer prevention.

Topics: 8-Hydroxy-2'-Deoxyguanosine; 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Cricetinae; Cytochrome P-450 Enzyme System; Deoxyguanosine; Disease Models, Animal; DNA Damage; Flavonoids; Gene Expression Regulation, Enzymologic; Immunoenzyme Techniques; Liver; Male; Mesocricetus; Mouth Mucosa; Mouth Neoplasms; Phenols; Tea; Xenobiotics