Showing papers on "7,12-Dimethylbenz[a]anthracene published in 2009"
Journal Article•
TL;DR: The chemopreventive efficacy of curcumin and piperine is probably due to their antilipidperoxidative and antioxidant potential as well as their modulating effect on the carcinogen detoxification process.
Abstract: Introduction: Oral carcinoma accounts for 40–50 percent of all cancers in India Tobacco chewing, smoking and alcohol consumption are the major risk factors associated with the high incidence of oral cancer in India Our aim was to investigate the chemopreventive potential of curcumin and piperine during 7,12-dimethylbenz[a]anthracene (DMBA) -induced hamster buccal pouch carcinogenesis Methods: Oral squamous cell carcinoma was developed in the buccal pouch of Syrian golden hamsters, by painting them with 05 percent DMBA in liquid paraffin, three times a week for 14 weeks The tumour incidence, tumour volume and burden were determined in the buccal pouches The status of phase II detoxification agents, lipid peroxidation and antioxidants were estimated by specific colorimetric methods
82 citations
TL;DR: It is demonstrated that orally administered ferulic acid has potent suppressing effect on cell proliferation during DMBA-induced skin carcinogenesis, probably due to its modulating effect on the status of lipid peroxidation, antioxidants and detoxication agents during DM BA-inducedskin carcinogenesis.
72 citations
TL;DR: Results support that VCD, but not DMBA, enhances ovotoxicity by increasing primordial to small primary follicles recruitment, and VCD is also a useful model chemical with which to elucidate signaling mechanisms involved in primordial follicle recruitment.
69 citations
TL;DR: Results demonstrate a conserved response in mice and rats for ovarian mEH involvement in DMBA bioactivation to its ovotoxic, 3,4-diol-1,2-epoxide form.
61 citations
TL;DR: It is shown that dietary GSPs inhibit chemical carcinogenesis in mouse skin and that the inhibition of skin tumorigenesis by G SPs is associated with the inhibited of inflammatory responses caused by tumor promoters.
Abstract: Grape seed proanthocyanidins (GSPs) possess anticarcinogenic activities. Here, we assessed the effects of dietary GSPs on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. Administration of dietary GSPs (0.2 and 0.5%, wt/wt) supplemented with control AIN76A diet resulted in significant inhibition of TPA-induced skin tumor promotion in C3H/HeN mice. The mice treated with GSPs developed a significantly lower tumor burden in terms of the percentage of mice with tumors (P < 0.05), total number of tumors per group (P < 0.01, n = 20) and total tumor volume per tumor-bearing mouse (P < 0.01-0.001) as compared with the mice that received the control diet. GSPs also delayed the malignant progression of papillomas into carcinomas. As TPA-induced inflammatory responses are used routinely as markers of skin tumor promotion, we assessed the effect of GSPs on biomarkers of TPA-induced inflammation. Immunohistochemical analysis and western blotting revealed that GSPs significantly inhibited expression of cyclooxygenase-2 (COX-2), prostaglandin E(2) (PGE(2)) and markers of proliferation (proliferating cell nuclear antigen and cyclin D1) in both the DMBA-initiated/TPA-promoted mouse skin and skin tumors. In short-term experiments in which the mouse skin was treated with acute or multiple TPA applications, we found that dietary GSPs inhibited TPA-induced edema, hyperplasia, leukocytes infiltration, myeloperoxidase, COX-2 expression and PGE(2) production in the mouse skin. The inhibitory effect of GSPs was also observed against other structurally different skin tumor promoter-induced inflammation in the skin. Together, our results show that dietary GSPs inhibit chemical carcinogenesis in mouse skin and that the inhibition of skin tumorigenesis by GSPs is associated with the inhibition of inflammatory responses caused by tumor promoters.
57 citations
TL;DR: The protective effects against skin cancer elicited by garlic in mice are believed to be due at least in part to the induction cellular defense systems.
49 citations
TL;DR: The chromosome variation accompanying the malignant growth was definitely non-random and involved preferentially 2 chromosome types, A2 and members of the D group, of the same type as reported earlier in DMBA-induced leukemias and sarcomas of the rat.
Abstract: The chromosomes were studied in direct preparations of 10 primary carcinomas, induced in rats by the application of 7,12-dimethylbenz(a)anthracene (DMBA) to the auricular skin. The chromosome variation accompanying the malignant growth was definitely non-random and involved preferentially 2 chromosome types, A2 and members of the D group. This chromosome pattern was of the same type as reported earlier in DMBA-induced leukemias and sarcomas of the rat. The present results support the conclusion that the inducing factor—not the tissue origin of the tumour—determines the karyotypic evolution.
35 citations
TL;DR: Oral administration of Withaferin-A to DMBA-painted hamsters not only completely prevented oral squamous cell carcinoma formation but also significantly prevented the alterations of p53 and bcl-2 expressions.
Abstract: Oral cancer, the fifth most frequent cancer worldwide, is a major health problem and accounts for highest morbidity and mortality in human populations. This form of cancer accounts for 40–50% of all cancers in developing countries including India. Despite recent advancement in the treatment, imaging and diagnosis of oral carcinoma, a 5-year survival and mortality rate for this cancer is still at 50%. Our aim was to study the protective effect of Withaferin-A on molecular pathogenesis of oral cancer by evaluating the immunoexpression of p53 and bcl-2 proteins. Oral squamous cell carcinoma was developed in the left buccal pouch of golden Syrian hamsters by painting with 0.5% 7,12-dimethylbenz(a)anthracene (DMBA), three times a week for 14 weeks. We observed 100% tumor formation with high tumor volume and burden in the DMBA alone painted hamsters as compared to control hamsters. We also observed markedly altered expression of p53 and bcl-2 proteins in tumor tissues of oral cancer bearing hamsters. Oral administration of Withaferin-A to DMBA-painted hamsters not only completely prevented oral squamous cell carcinoma formation but also significantly prevented the alterations of p53 and bcl-2 expressions. Our results thus suggest that Withaferin-A has significant protective role against DMBA induced molecular alterations in the buccal mucosa of golden Syrian hamsters.
33 citations
TL;DR: Repeated carcinogen applications caused the appearance of numerous papillomas, keratoacanthomas and squamous cell carcinomas in Swiss, A, ASW/SN Balb/c and C57B1 mice, New Zealand and outbred laboratory rabbits, and in AKR mice and Hormel mini pigs unresponsive.
Abstract: The pattern of development of tumours was studied in several mice strains, rabbits and pigs. Repeated carcinogen applications caused the appearance of numerous papillomas, keratoacanthomas and squamous cell carcinomas in Swiss, A, ASW/SN, Balb/c and C57B1 mice, New Zealand and outbred laboratory rabbits. AKR mice were only little sensitive and Hormel mini pigs unresponsive. Initiation with 7,12-dimethylbenz (a) — anthracene and promotion with croton oil produced in Swiss, A, Balb/c and C3H mice as well as New Zealand rabbits a large number of squamous papillomas. Pigmented or adnexal tumours were not observed, and only a few dermal fibromas and fibrosarcomas.
32 citations
Journal Article•
TL;DR: The results indicate that the protective effect of Withaferin-A is probably due to its anti-lipid peroxidative and antioxidant functions as well as modulating effect on carcinogen detoxication during DMBA-induced oral carcinogenesis.
Abstract: With an aim to investigate the protective effect of Withaferin-A on 7,12-dimethylbenz[a]anthracene (DMBA) induced oral carcinogenesis in Syrian golden hamsters, tumour incidence, tumour volume and tumour burden and status of detoxication agents, lipid peroxidation and antioxidants in DMBA administered (3 times/week for 14 weeks) hamsters were assessed. Hundred percent tumour formation in DMBA alone administered animal was observed. Oral administration of Withaferin-A (20 mg/kg body weight) to DMBA administered animals for 14 weeks completely prevented the tumour incidence, tumour volume and tumour burden. Also, Withaferin-A showed significant anti-lipid peroxidative and antioxidant properties and maintained the status of phase-I and phase-II detoxication agents during DMBA-induced oral carcinogenesis. The results thus indicate that the protective effect of Withaferin-A is probably due to its anti-lipid peroxidative and antioxidant functions as well as modulating effect on carcinogen detoxication during DMBA-induced oral carcinogenesis.
31 citations
TL;DR: The results suggest that genistein has potent antigenotoxic effect against DMBA-induced genotoxicity, which is a crucial step in cancer initiation.
TL;DR: These studies demonstrate that the VCD-treated rat can be used as a model for peri- and post-menopause and develop a modelfor ovarian cancer in which ovarian neoplasms were chemically induced in an animal that was follicle depleted, but retained residual ovarian tissue.
TL;DR: Oral administration of piperine by gastric gavage significantly prevented the formation of skin tumors during DMBA-induced mouse skin carcinogenesis and brought back the status of phase I and phase II detoxification agents, lipid peroxidation by-products and antioxidants to near normal range in DMBA treated mice.
TL;DR: The results from this study in combination with previous data suggest that the chemopreventive effects of GLN are exerted by enhancing the antioxidant status of the body and activation of apoptosis.
TL;DR: The global SSH approach revealed that mRNAs of genes related to xenobiotic metabolism, immune processes and cytoskeleton dynamics were differentially expressed in DMBA-exposed eel livers, highlighting the complexity in the response observed in fish exposed to a genotoxic agent and providing directions for new biomarker development.
TL;DR: Analysis of the skin 6 h after TPA treatment showed that the TPA-induced promotion of skin edema, inflammatory leukocyte infiltration, COX-2 expression and PGE(2) production was significantly lower in the skin of the IL-12-KO mice than their wild-type counterparts.
Abstract: Interleukin (IL)-12 deficiency exacerbates tumorigenesis in ultraviolet (UV) radiation-induced skin. Here, we assessed the effects of IL-12 deficiency on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated mouse skin. Using this two-stage chemical carcinogenesis protocol, we found that the development of DMBA/TPA-induced skin tumors was diminished in IL-12p40-knockout mice than in their wild-type counterparts. At the termination of the experiment (at 24 weeks), the skin tumor incidence and tumor multiplicity were significantly lower (P < 0.005) in interleukin-12-knockout (IL-12 KO) mice than in their wild-type counterparts, as was the malignant transformation of DMBA/TPA-induced papillomas to carcinomas (P < 0.01). Analysis of samples collected at the termination of the experiments for biomarkers of inflammation by immunohistochemical analysis, western blotting, enzyme-linked immunosorbent assay and real-time polymerase chain reaction revealed significantly lower levels of cyclooxygenase-2 (COX-2), prostaglandin (PG) E2, proliferating cell nuclear antigen, cyclin D1 and the proinflammatory cytokines (tumor necrosis factor-α, IL-1β and IL-6) in the DMBA/TPA-treated tumors and tumor-uninvolved skin of IL-12 KO mice than the skin and tumors of DMBA/TPA-treated wild-type mice. Analysis of the skin 6 h after TPA treatment showed that the TPA-induced promotion of skin edema, inflammatory leukocyte infiltration, COX-2 expression and PGE2 production was significantly lower in the skin of the IL-12-KO mice than their wild-type counterparts. These results indicate that DMBA/TPA-induced skin tumor development differs from UVB-induced skin tumor development in that endogenous IL-12 acts to inhibit UVB-induced skin tumor development and malignant progression of the skin tumors to carcinoma. In the case of DMBA/TPA-induced skin tumor development, the endogenous IL-12 modulates the tumor promoter stimulation of inflammatory responses.
TL;DR: In rats administered DES from 0 to 14 and 0 to 5 days after birth there was protection from development of MCs and PLs, and serum levels of both estrogen and progesterone were significantly lower than in the control animals at 100 days afterBirth.
Abstract: The aim of this study was to investigate the effects of neonatal administration of a relatively high dose of diethylstilbestrol (DES) on the induction of mammary carcinomas (MCs) and benign proliferative lesions (PLs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Three different terms of daily administration of DES (10 microg) were used: 0-14, 0-5, and 6-14 days after birth. Control animals were administered solvent (oil) alone once daily from 0 to 14 days after birth. Rats were given DMBA (10 mg) at 50 days after birth. All rats administered DES showed persistent estrus and anovulatory ovaries. In rats administered DES from 0 to 14 and 0 to 5 days after birth there was protection from development of MCs and PLs, and serum levels of both estrogen and progesterone were significantly lower than in the control animals at 100 days after birth. In rats administered DES from 6 to 14 days after birth, the incidence of MCs was equal to that of the control animals (100%), and the number of PLs was significantly higher than in the control animals. The critical period for exposure to endocrine disruptors, such as DES, affecting the induction of MCs and PLs may be from 0 to 5 days after birth.
TL;DR: The present findings provide a better understanding of the molecular alteration that occur during mammary carcinogenesis and suggest the importance of PEP‐19 overexpression in the very early stage of mammary cancerogenesis.
Abstract: 7,12-Dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinoma is a well-recognized model; however, the genetic alterations during its carcinogenesis have yet to be determined. We used laser capture microdissection to specifically isolate cells from terminal end buds (TEBs), the origin of carcinoma, at 2 weeks after sesame oil treatment (control) or DMBA treatment (DMBA-TEBs), ductal carcinoma in situ (DCIS) and invasive mammary carcinoma (MC). Using an oligonucleotide microarray representing 20,600 rat probe sequences, we analyzed gene expression profiles and validated mRNA and protein levels of genes of interest byreal-time quantitative PCR and immunohistochemistry. The number of differentially expressed genes dramatically increased from DMBA-TEBs (63) to DCIS (798) and MC (981). Only the expression of PEP-19, an anti-apoptotic gene, showed significant increases in DMBA-TEBs (4-fold), DCIS (10-fold) and MC (16-fold). MMP-13 expression was increased markedly in DCIS (19-fold) and MC (61-fold) while OPN expression was increased 6-fold in DCIS and 8-fold in MC. MMP-7 expression was increased 4-fold in MC. Nidogen-1; a participant in the assembly of basement membranes, TSP-2; an inhibitor of angiogenesis and COUP-TFI; a transcription repressor showed significant decreases in DCIS (4-, 9- and 17-fold, respectively) and MC (10-, 37- and 100-fold). Network analyses with IPA software revealed that the most significant network included Akt groups in DCIS and ERK groups in MC. The present findings provide us with a better understanding of the molecular alteration that occur during mammary carcinogenesis and suggest the importance of PEP-19 overexpression in the very early stage of mammary carcinogenesis. © 2009 UICC
TL;DR: Results indicate that prepubertal exposure to TBBPA raises susceptibility to thyroid and urinary bladder tumorigenesis in rats, and causes of the effect on thyroid carcinogenesis might be direct and/or indirect hormonal actions.
TL;DR: 3-Nitrobenzanthrone and N-OH-3-ABA were found to be inactive as either tumour initiators or complete carcinogens in mouse skin over a dose range of 25-400nmol, indicating that initial DNA adduct levels do not parallel tumour initiating activity.
TL;DR: The data suggest that although E2 status does not effect soy-mediated AhR degradation, it modulates the effects of soy on many genes, including CYP1A1.
TL;DR: It is suggested that administration of a large dose of OP for a long period may have had a minimal effect on mammary carcinogenesis in male rats.
Abstract: We previously reported that a neonatal administration of diethylstilbestrol or 17beta-estradiol affected the mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rats. The aim of this present study was to investigate the effects of 4-n-octylphenol (OP), a weak estrogenic disruptor, on the induction of mammary carcinomas (MC) and benign proliferative lesions (PL) induced by DMBA in rats. All female rats were administered at 0, 0.1, 10, 100, and 1,000 microg OP once at birth, given 10 mg DMBA at 50 days after birth, and thereafter underwent necropsy at 351 days after birth. All male rats were given 10 mg DMBA at 28, 42, and 56 days after birth, and 0, 10, 100, and 1,000 ppm OP fed from day 70-153; they underwent necropsy at 153 days after birth. Neonatal single administration of OP in female rats showed no effects such as persistent estrus, anovulatory ovaries, or PL. A slight increase in numbers of rats with MC occurred at the highest dosage. Feeding a large dose of OP for a long period in male rats induced atrophy of testes and slightly increased numbers of affected MC but not increased numbers of males while it showed no effects on PL. These results suggested that administration of a large dose of OP for a long period may have had a minimal effect on mammary carcinogenesis in male rats.
Journal Article•
TL;DR: The results evidence the protective in vivo effects of monoterpenes on an experimentally induced oxidative stress and suggest that dietary supplementation would be beneficial for the prevention of free radical damage.
Abstract: SUMMARY This study was carried out to investigate the potential antioxidant effects of 2 monoterpenes, linalool and d-limonene, in female rats orally treated or not with dimethylbenz(a)anthracene (DMBA). For this purpose, 70 female Wistar Albino rats (7-8 weeks old) were randomly divided into 10 equal groups according to the modalities of monoterpene dietary supplementation and/or oral DMBA (65 mg/kg) treatment. Negative controls were not supplemented and untreated, positive controls received only DMBA, whereas all the other groups were fed with diets enriched by 5% limonene or linalool for 150 days and received no DMBA (groups 2 and 3) or DMBA administration 15 days after (groups 5 and 6), in the same time (groups 7 and 8) or 6 days before (groups 9 and 10) the beginning of terpene supplementation. Plasma concentrations of MDA (considered as a marker of oxidative stress) were measured in all animals on days 15, 30, 45, 60, 75 and 150. This marker was dramatically increased by DMBA treatment alone then gradually declined. By contrast, the dietary monoterpene supplementation has induced significant decreases of spontaneous MDA formation and also has markedly inhibited DMBA-induced lipid peroxidation, the best protocol being initiation of supplementation before DMBA administration. Furthermore, linalool has appeared as a more potent antioxidant than limonene. These results evidence the protective in vivo effects of monoterpenes on an experimentally induced oxidative stress and suggest that dietary supplementation would be beneficial for the prevention of free radical damage.
TL;DR: The present study attempts to identify the effects on DMBA-induced tumor growth of diets rich in fat and of the highly selective COX-2 inhibitor Celecoxib, which has been claimed to offer substantial protection against carcinogenesis.
Abstract: The effects of diet, of non-steroidal anti-inflammatory drugs, or of their combination on carcinogenesis continue to be a case for controversy. Diets that are high in fat have been linked to increased risk of various tumors. At the same time there is substantial, but not conclusive, evidence that the risk of breast and colon cancer correlates with total fat intake rather than a specific type of fat. On the other hand, non-steroidal anti-inflammatory drugs (NSAIDs) have been studied extensively because they appear to delay or inhibit the development of malignant and pre-malignant lesions. 7,12-Dimethylbenz-(a)-anthracene (DMBA) has been used for a long time to induce carcinogenesis in a number of rat animal models. The present study attempts to identify the effects on DMBA-induced tumor growth (a) of diets rich in fat and (b) of the highly selective COX-2 inhibitor Celecoxib, which has been claimed to offer substantial protection against carcinogenesis.
TL;DR: The results indicate that DAG-rich oil has promoting potential for skin carcinogenesis, and thus, further investigations of its tumor-promoting potential in other organs are warranted.
Journal Article•
TL;DR: In this paper, the authors used aqueous extract of Ginger concentration (120 mg/ml) as a protective agent against the ovotoxicity of the ovary of an immature female rat.
Abstract: The rhizome of Ginger (Zingiber officinale Rosc.) has been used as a spice and for medical purposes in Asian, Indian, and Arabic herbal traditions since ancient time. Recently, it has gained considerable attention as a botanical dietary due to its active biological constituents of phenolic substances ([6]-gingerol, and [6]-paradol) that possess anti-inflammatory, and anti-oxidative properties. It also exerts substantial anti-carcinogenic activities. The present study used aqueous extract of Ginger concentration (120 mg/ml) as a protective agent against the ovotoxicity of the ovary of immature female rat. The study used the chemical 7, 12-dimethylbenz[a]anthracene (DMBA) as a potent carcinogen causes destruction of different ovarian follicles to form the ovotoxicity. The histopathological observations of DMBA treated group revealed the following: 1- edematous ovaries leading to increment of their sizes, 2- pore ovarian cycle; 3- increase the number of atretic follicular in comparing with the still lived ones; 4- numerous large corpora lutea; 5- congested blood vessels; 6- stromal hyperplasia. The histochemical studies of the total protein have been given from sections stained with mercuric-bromophenol blue. DMBA treated group showed pail blue color at the granulose cells of the different follicles, ovarian medulla and corpus lutea indicating decrement of the protein content except some sites of high content may be indicate sites of active neoplasia. The histopathological and histochemical observations of DMBA and Ginger treated group exhibited a degree of the ovarian tissue improvement in which the size of the ovaries decreased, and the ovarian follicles were in different stages of development and the appearance of protein seems to be as control. Uses of Ginger as a protective substance against the ovotoxic ovarian tissue revealed some degree of improvement at this stage of experiment.
Journal Article•
TL;DR: It is suggested that equol modulates the CYP1A1 through a reduction of AhR expression in mice treated with DMBA, similar to its effect on CYP 1A1.
Abstract: Present study was investigated the hepatic effects of equol on the 7,12-dimethylbenz(a)anthracene (DMBA)-induced enzymatic activity and expression of CYP1Al and CYP1B1 in mice. Equol was administered orally at 5 and 25 ㎎/㎏ BW for 4 weeks. Subsequently, mice pretreated with equol received DMBA intragastrically twice a week for 2 weeks. DMBA induced CYP1 activity as well as the expression of CYP1A1 and CYP1B1. Each of these effects was significantly reduced by equol in dose-dependent manner (p＜0.05). Equol also reduced the relative AhR mRNA expression, similar to its effect on CYP1A1. These results suggest that equol modulates the CYP1A1 through a reduction of AhR expression in mice treated with DMBA.