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Frontiers in Bioscience (Scholar... Jan 2011Alpha-santalol, a naturally occurring terpenoid, has been shown to have chemopreventive effects on both 7, 12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O-... (Review)
Review
Alpha-santalol, a naturally occurring terpenoid, has been shown to have chemopreventive effects on both 7, 12-dimethylbenz(a)anthracene (DMBA)-initiated and 12-O- tetradecanoylphorbol-13-acetate (TPA)-promoted skin cancer development in CD-1 and SENCAR mice, and UVB-induced skin cancer developments in SKH-1 hairless mice in a concentration-dependent manner. Studies have demonstrated that α-santalol could be effective against skin carcinogenesis through both induction of apoptosis via caspase activation together with dissipation of mitochondria membrane potential and cytochrome c release in A431 cells, and inhibition of cell growth via induction of G2/M phase arrest in both A431 cells and melanoma UACC-62 cells by altering multiple cell cycle regulatory proteins and complexes. This review summarizes the chemopreventive effects and molecular mechanisms of α-santalol on skin cancer development in both animal models and skin cancer cell lines.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Cell Cycle; Cell Line, Tumor; Drugs, Chinese Herbal; Humans; Mice; Mice, Mutant Strains; Phytotherapy; Plant Oils; Polycyclic Sesquiterpenes; Santalum; Sesquiterpenes; Skin Neoplasms; Tetradecanoylphorbol Acetate
PubMed: 21196411
DOI: 10.2741/s186 -
Experimental Biology and Medicine... Jul 2011At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial... (Review)
Review
At birth, the mammalian ovary contains a finite number of primordial follicles, which once depleted, cannot be replaced. Xenobiotic exposures can destroy primordial follicles resulting in premature ovarian failure and, consequently, early entry into menopause. A number of chemical classes can induce premature ovarian failure, including environmental, chemotherapeutic and industrial exposures. While our knowledge on the mechanistic events that occur in the ovary with chemical exposures is increasing, our understanding of the ovary's capacity to metabolize such compounds is less established. This review will focus on three chemicals for which information on ovarian metabolism is known: trichloroethylene, 7,12-dimethylbenz[a]anthracene and 4-vinylcyclohexene. The current state of understanding of ovarian bioactivation and detoxification processes for each will be described.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Cyclohexenes; Female; Inactivation, Metabolic; Ovary; Primary Ovarian Insufficiency; Trichloroethylene; Xenobiotics
PubMed: 21616964
DOI: 10.1258/ebm.2011.011051 -
Asian Pacific Journal of Cancer... Aug 2022Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer, showing poor prognosis and high mortality. Meanwhile, cancer metabolism is an essential...
BACKGROUND AND AIM OF THE STUDY
Oral squamous cell carcinoma (OSCC) is the most common form of oral cancer, showing poor prognosis and high mortality. Meanwhile, cancer metabolism is an essential contributor to its progression and response to treatment. This research aims to investigating the effect of a glucose-rich and glucose-free diet on the progress of oral squamous cell carcinoma induced in hamsters.
MATERIALS AND METHODS
forty Syrian Hamsters were incubated in two groups. The first one consisted of twenty hamsters, in which the carcinogenic material (DMBA) was applied in the buccal pouch of the hamster three days per week with a glucose-rich diet). The second one was composed of twenty hamsters, in which the carcinogenic material (DMBA) was applied in the buccal pouch three days per week with a glucose-free diet). Hamsters in both groups were sacrificed in groups of five hamsters at a time and at intervals (two weeks, six weeks, ten weeks, and Fourteen weeks). A histological study was performed after conventional staining with hematoxylin and eosin was done.
RESULTS
After two weeks of the experiment hyperplasia, mild dysplasia, and moderate dysplasia were recorded in hamster buccal pockets with a glucose-rich diet, and after six weeks moderate dysplasia, severe dysplasia, and carcinomas in situ were recorded, after ten weeks severe dysplasia, carcinomas in situ, and OSCC, after fourteen weeks OSCC were recorded. While with a glucose-free diet Hyperkeratosis, hyperplasia, and mild dysplasia were observed after a two-week the experiment, after six weeks, mild dysplasia, moderate dysplasia, and severe dysplasia were recorded, after ten weeks, moderate dysplasia, severe dysplasia, and carcinoma in situ, after fourteen weeks Severe dysplasia, carcinoma in situ, and OSCC were reported.
CONCLUSION
our results showed that a glucose-free diet slightly prevents oral squamous cell carcinoma, It may be a supportive treatment in addition to conventional cancer treatment.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogenesis; Carcinogens; Carcinoma in Situ; Carcinoma, Squamous Cell; Cricetinae; Glucose; Head and Neck Neoplasms; Humans; Hyperplasia; Mesocricetus; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck
PubMed: 36037144
DOI: 10.31557/APJCP.2022.23.8.2857 -
GeroScience Apr 2019There is significant overlap between the cellular and molecular mechanisms of aging and pathways contributing to carcinogenesis, including the role of genome maintenance... (Review)
Review
There is significant overlap between the cellular and molecular mechanisms of aging and pathways contributing to carcinogenesis, including the role of genome maintenance pathways. In the field of geroscience analysis of novel genetic mouse models with either a shortened, or an extended, lifespan provides a unique opportunity to evaluate the synergistic roles of longevity assurance pathways in cancer resistance and regulation of lifespan and to develop novel targets for interventions that both delay aging and prevent carcinogenesis. There is a growing need for robust assays to assess the susceptibility of cancer in these models. The present review focuses on a well-characterized method frequently used in cancer research, which can be adapted to study resilience to genotoxic stress and susceptibility to genotoxic stress-induced carcinogenesis in geroscience research namely, chemical carcinogenesis induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA). Recent progress in understanding how longer-living mice may achieve resistance to chemical carcinogenesis and how these pathways are modulated by anti-aging interventions is reviewed. Strain-specific differences in sensitivity to DMBA-induced carcinogenesis are also explored and contrasted with mouse lifespan. The clinical relevance of inhibition of DMBA-induced carcinogenesis for the pathogenesis of mammary adenocarcinomas in older human subjects is discussed. Finally, the potential role of insulin-like growth factor-1 (IGF-1) in the regulation of pathways responsible for cellular resilience to DMBA-induced mutagenesis is discussed.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Aging; Animals; Carcinogenesis; DNA Damage; Disease Models, Animal; Female; Geriatrics; Humans; Longevity; Male; Mammary Neoplasms, Experimental; Mice; Rats, Sprague-Dawley; Research; Rodentia
PubMed: 31037472
DOI: 10.1007/s11357-019-00064-4 -
The Journal of Investigative Dermatology Jul 1976Skin tumors chemically induced in mice have provided an important experimental model for studying carcinogenesis and for bioassaying carcinogenic agents. The information... (Review)
Review
Skin tumors chemically induced in mice have provided an important experimental model for studying carcinogenesis and for bioassaying carcinogenic agents. The information obtained from this model suggests that the events leading to tumor formation can be divided into at least two stages, initiation and promotion. A single small dose of carinogen produces initiation which appears to be irreversible. These initiating agents may have to be metabolically activated and can interact with cellular macromolecules. The extent to which they bind to DNA correlates well with their carcinogenicity. Increased DNA replication at the time of or during the first day after these agents have been applied appears to enhance carcinogenesis. Unlike initiation, promotion appears to be reversible and the promoting agents must be applied repeatedly before tumors are formed. Promoters interact with membranes, stimulate and alter genetic expression, and increase the rate of cell proliferation. The knowledge gained from these studies in mouse skin has immeasurably helped the entire field of chemical carcinogenesis. But efforts to determine the cellular and molecular mechanisms involved in the carcinogenic process, particularly in the skin, have been hampered by the difficulties of working on whole animals and by the special problems associated with the biologic and biochemical methods required for this target organ. Such problems, however, can be solved by the use of cell cultures of mouse epidermis which can metabolize and bind carcinogens just as is done in vivo. The fact that epidermal cells in vitro proliferate synchronously should facilitate the study of the relation between the cell cycle and carcinogenesis. These cells repair chemically induced DNA damage by at least two mechanisms, excision repair and base-specific repair. When epidermal cells in vitro are exposed to promoting agents, a proliferative response analogous to that in vivo is elicited, apparently mediated through control of polyamine metabolism. Neoplastic transformation has been induced in these cultures by known skin carcinogens.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Aryl Hydrocarbon Hydroxylases; Benzopyrenes; Carcinogens; Cell Division; Cells, Cultured; Chemical Phenomena; Chemistry; Croton Oil; Culture Media; DNA, Neoplasm; Disease Models, Animal; Drug Synergism; Kinetics; Methylnitronitrosoguanidine; Mice; Ornithine Decarboxylase; RNA, Neoplasm; Skin Neoplasms
PubMed: 819592
DOI: 10.1111/1523-1747.ep12513040 -
The Journal of Investigative Dermatology Jan 1994Because of its special aroma, green tea is a popular beverage consumed by some human populations worldwide. In recent years, many laboratory studies have shown that in a... (Review)
Review
Because of its special aroma, green tea is a popular beverage consumed by some human populations worldwide. In recent years, many laboratory studies have shown that in a variety of animal tumor bioassay systems the administration of green tea, specifically the polyphenolic fraction isolated from green tea leaves (green tea polyphenols), affords protection against cancer induction. In mouse skin tumor bioassay systems, topical application of green tea polyphenols to skin has been shown to result in protection against a) 3-methylcholanthrene-induced skin tumorigenicity, b) 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin tumor initiation, c) 12-O-tetradecanoylphorbol-13-acetate and other tumor promoters caused tumor promotion in DMBA-initiated skin, and d) benzoyl peroxide- and 4-nitroquinoline N-oxide caused enhanced malignant progression of nonmalignant lesions. Green tea extract has also been shown to cause partial regression of established skin papillomas in mouse. Similarly, chronic oral feeding of green tea polyphenols or water extract of green tea has also been shown to result in the protection against both chemical carcinogen- and ultraviolet B radiation-induced skin tumorigenicity. Collectively these data suggest that green tea possesses significant chemopreventive effect against each stage of carcinogenesis, and that it may be useful against inflammatory responses associated with the exposure of skin to chemical tumor promoters as well as to solar radiation. Available data regarding the mechanism by which green tea affords these diversified effects is discussed.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Topical; Animals; Antineoplastic Agents; Dermatitis; Humans; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Skin Neoplasms; Tea; Tetradecanoylphorbol Acetate
PubMed: 8288907
DOI: 10.1111/1523-1747.ep12371720 -
Environmental Health Perspectives Mar 1983Mammary carcinomas induced by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) to young virgin rats arise from undifferentiated terminal ductal structures... (Review)
Review
Mammary carcinomas induced by the administration of 7,12-dimethylbenz(a)anthracene (DMBA) to young virgin rats arise from undifferentiated terminal ductal structures called terminal end buds (TEBs). TEBs that normally differentiate into alveolar buds (ABs) and lobules under the influence of DMBA develop intraductal proliferations which progress to carcinoma. The high susceptibility of the young virgin rat TEBs to neoplastic transformation is due to its large proliferative compartment, with cells cycling every 10 hr, and to a higher (3)H-DMBA uptake. Progressive differentiation of TEBs into ABs and lobules or their regression to terminal ducts (TDs) is seen with aging. Complete differentiation of the gland is attained only through pregnancy and lactation. The greater differentiation of the gland is manifested as permanent structural changes, consisting in the disappearance of TEBs and in a diminution of the number of TDs due to their differentiation into ABs and lobules. This greater differentiation results in a diminished or total refractoriness of the gland to the carcinogen because ABs and lobules have a lower proliferative compartment and a longer cell cycle than TEBs and TDs. Cells of parous rats have both in vivo and in vitro a lower DMBA-DNA binding capacity, a lower DNA synthesis and a greater ability to repair DMBA damaged DNA than cells of young virgin rats. The more efficient DNA repair capacity of the parous rat mammary gland is demonstrated by the induction of unscheduled DNA synthesis and a removal of DMBA-DNA adducts.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Aging; Animals; Binding Sites; Carcinogens; Cell Differentiation; Cell Transformation, Neoplastic; Cells, Cultured; DNA; DNA Repair; Female; Hormones; In Vitro Techniques; Kinetics; Mammary Neoplasms, Experimental; Polycyclic Compounds; Rats; Rats, Inbred Strains
PubMed: 6403347
DOI: 10.1289/ehp.8349185 -
Toxicology and Applied Pharmacology Jun 2012The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the... (Review)
Review
The mammalian ovary is a heterogeneous organ and contains oocyte-containing follicles at varying stages of development. The most immature follicular stage, the primordial follicle, comprises the ovarian reserve and is a finite number, defined at the time of birth. Depletion of all follicles within the ovary leads to reproductive senescence, known as menopause. A number of chemical classes can destroy follicles, thus hastening entry into the menopausal state. The ovarian response to chemical exposure can determine the extent of ovotoxicity that occurs. Enzymes capable of bioactivating as well as detoxifying xenobiotics are expressed in the ovary and their impact on ovotoxicity has been partially characterized for trichloroethylene, 7,12-dimethylbenz[a]anthracene, and 4-vinylcyclohexene. This review will discuss those studies, as well as illustrate where knowledge gaps remain for chemicals that have also been established as ovotoxicants.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Aging; Animals; Benzhydryl Compounds; Carcinogens; Cyclohexenes; Environmental Exposure; Environmental Pollutants; Estrogens, Non-Steroidal; Female; Humans; Inactivation, Metabolic; Methoxychlor; Oocytes; Ovarian Diseases; Ovarian Follicle; Phenols; Phthalic Acids; Polychlorinated Dibenzodioxins; Trichloroethylene; Xenobiotics
PubMed: 22531813
DOI: 10.1016/j.taap.2012.04.009 -
PloS One May 2011Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also...
Oxygen serves as an essential factor for oxidative stress, and it has been shown to be a mutagen in bacteria. While it is well established that ambient oxygen can also cause genomic instability in cultured mammalian cells, its effect on de novo tumorigenesis at the organismal level is unclear. Herein, by decreasing ambient oxygen exposure, we report a ∼50% increase in the median tumor-free survival time of p53-/- mice. In the thymus, reducing oxygen exposure decreased the levels of oxidative DNA damage and RAG recombinase, both of which are known to promote lymphomagenesis in p53-/- mice. Oxygen is further shown to be associated with genomic instability in two additional cancer models involving the APC tumor suppressor gene and chemical carcinogenesis. Together, these observations represent the first report directly testing the effect of ambient oxygen on de novo tumorigenesis and provide important physiologic evidence demonstrating its critical role in increasing genomic instability in vivo.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Base Sequence; Blotting, Western; Carcinogens; DNA Primers; Female; Genomic Instability; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Neoplasms, Experimental; Oxygen; Skin Neoplasms
PubMed: 21589870
DOI: 10.1371/journal.pone.0019785 -
The Journal of Investigative Dermatology Feb 2021Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium...
Nonmelanoma skin cancer such as cutaneous squamous cell carcinoma (cSCC) is the most common form of cancer and can occur as a consequence of DNA damage to the epithelium by UVR or chemical carcinogens. There is growing evidence that the complement system is involved in cancer immune surveillance; however, its role in cSCC remains unclear. Here, we show that complement genes are expressed in tissue from patients with cSCC, and C3 activation fragments are present in cSCC biopsies, indicating complement activation. Using a range of complement-deficient mice in a two-stage mouse model of chemically-induced cSCC, where a subclinical dose of 7,12-dimethylbenz[a]anthracene causes oncogenic mutations in epithelial cells and 12-O-tetradecanoylphorbol-13-acetate promotes the outgrowth of these cells, we found that C3-deficient mice displayed a significantly reduced tumor burden, whereas an opposite phenotype was observed in mice lacking C5aR1, C5aR2, and C3a receptor. In addition, in mice unable to form the membrane attack complex, the tumor progression was unaltered. C3 deficiency did not affect the cancer response to 7,12-dimethylbenz[a]anthracene treatment alone but reduced the epidermal hyperplasia during 12-O-tetradecanoylphorbol-13-acetate-induced inflammation. Collectively, these data indicate that C3 drives tumorigenesis during chronic skin inflammation, independently of the downstream generation of C5a or membrane attack complex.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Carcinogens; Carcinoma, Squamous Cell; Complement Activation; Complement C3; Complement C5; Complement Membrane Attack Complex; Disease Models, Animal; Disease Progression; Humans; Mice; Mice, Knockout; Mice, Transgenic; Neoplasms, Experimental; Receptor, Anaphylatoxin C5a; Receptors, Complement; Signal Transduction; Skin; Skin Neoplasms; Tumor Escape
PubMed: 32682912
DOI: 10.1016/j.jid.2020.06.025