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Anti-cancer Agents in Medicinal... 2022Kolaviron (KV) is a flavonoid-rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on...
BACKGROUND
Kolaviron (KV) is a flavonoid-rich portion obtained from Garcinia kola seeds with a number of reported pharmacological effects. However, its ameliorative effects on 7,12-Dimethylbenzanthracene (DMBA)-induced mammary damage has not been fully investigated, despite the reported use of the seeds in the treatment of inflammatory related disorders.
OBJECTIVE
To evaluate the ameliorative effects of KV on DMBA-induced mammary damage in female Wistar rats.
METHODS
Forty-nine (49) female Wistar rats were randomly assigned into seven groups of seven rats each. DMBA was administered orally to rats in five of the groups as a single dose of 80 mg/kg body wt while the remaining two groups received the vehicle. The rats were palpated weekly for 3 months to monitor tumor formation. After 3 months of DMBA administration, 1 ml of blood was collected to assay for estrogen receptor- α (ER-α) level. Thereafter, the vehicle (dimethyl sulfoxide) was daily administered to the negative control and positive control groups for the 14 days duration of the experiment while three groups were each given a daily oral dose of 50, 100, and 200 mg/kg body wt of KV for the duration of the experiment. The last DMBA-induced group received 10 mg/kg body wt of the standard drug tamoxifen twice a week, and the remaining DMBA-free group received 200 mg/kg body wt KV. Subsequently, the animals were humanely sacrificed, and ER-α, sialic acids, sialidase, sialyltransferase levels were assayed in blood and mammary tissues followed by histopathological examinations.
RESULTS
Significantly higher levels of estrogen receptor-α (ER-α), formation of lobular neoplastic cells, epithelial hyperplasia, lymphocyte infiltration, and increased sialylation were detected in DMBA-induced rats. Treatment with KV at 50, 100, and 200 mg/kg body weight resulted in a significant (p<0.05) decrease in ER-α level, free serum sialic acid (21.1%), the total sialic acid level of the mammary tissue (21.57%), sialyltransferase activity (30.83%) as well as mRNA level of the sialyltransferase gene (ST3Gal1) were observed after KV interventions.
CONCLUSION
The findings suggest that KV could be further explored in targeting DMBA-induced mammary damage implicated in mammary carcinogenesis.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Administration, Oral; Animals; Body Weight; Breast; Dose-Response Relationship, Drug; Estrogen Receptor alpha; Female; Flavonoids; Rats; Rats, Wistar; Structure-Activity Relationship
PubMed: 34225638
DOI: 10.2174/1871520621666210322101232 -
Human & Experimental Toxicology Jul 2020Cancer continues to be a major cause of mortality globally. Zebrafish present suitable models for studying the mechanisms of genotoxic carcinogens. The aim of this study... (Comparative Study)
Comparative Study
Cancer continues to be a major cause of mortality globally. Zebrafish present suitable models for studying the mechanisms of genotoxic carcinogens. The aim of this study was to investigate the interaction between oxidant-antioxidant status, apoptosis and immunity in zebrafish that were exposed to three different genotoxic carcinogens methylnitrosourea, dimethylbenzanthracene, benzoapyrene and methylnitrosourea + dimethylbenzanthracene starting from early embryogenesis for 30 days. Lipid peroxidation, nitric oxide levels, superoxide dismutase and glutathione--transferase activities and mRNA levels of apoptosis genes , , , and immunity genes , and were evaluated. The disruption of the oxidant-antioxidant balance accompanied by altered expressions of apoptotic and immunity related genes were observed in different levels according to the carcinogen applied. Noteworthy, expressions decreased in all carcinogen-exposed groups. Our results will provide basic data for further carcinogenesis research in zebrafish models.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Apoptosis; Apoptosis Regulatory Proteins; Benzo(a)pyrene; Carcinogens; Embryo, Nonmammalian; Glutathione Transferase; Interferon-gamma; Methylnitrosourea; Nitric Oxide; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase; Zebrafish; Zebrafish Proteins
PubMed: 32054343
DOI: 10.1177/0960327120905961 -
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 -
The Journal of Toxicological Sciences 2022Testicular Leydig cells produce testosterone through the participation of steroidogenic proteins. The CYP1B1 enzyme has been shown to catalyze...
Testicular Leydig cells produce testosterone through the participation of steroidogenic proteins. The CYP1B1 enzyme has been shown to catalyze 7,12-dimethylbenzanthracene (DMBA), a representative polycyclic aromatic hydrocarbon. We hypothesized that exposure to DMBA causes Leydig cell cytotoxicity through activation of CYP1B1. Leydig cells were exposed to various concentrations of DMBA for the induction of CYP1B1 expression and activity. The status of CYP1B1 function was monitored by evaluation of cytotoxicity-mediated cell death. Our data show that exposure to DMBA causes cytotoxicity in Leydig cells by CYP1B1 activation. DMBA evoked a significant increase in the generation of reactive oxygen species (ROS) by which the depolarization of mitochondrial membrane potential (MMP) is initiated and caspase-3 activation is augmented. The knockdown of CYP1B1 expression resulted in the suppression of DMBA-induced apoptosis via reduced p53 activation and caspase-3 activation, suggesting that a final metabolite of DMBA (i.e., DMBA-DE) bioactivated by CYP1B1 induces p53 activation by binding to DNA and subsequently causing apoptosis via caspase-3 activation. This finding provides evidence for constitutive expression of CYP1B1 in Leydig cells, which is a trait that only requires an initiating signal for its activity. Further research on CYP1B1 activation-provoked steroid metabolism in Leydig cells may provide decisive clues for elucidating its innate function.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Apoptosis; Caspase 3; Cytochrome P-450 CYP1B1; Humans; Leydig Cells; Male; Tumor Suppressor Protein p53
PubMed: 35908932
DOI: 10.2131/jts.47.317 -
Methods in Cell Biology 2021Every year, over 2 million women are diagnosed with breast cancer. Although considerable progress was made within the last years in cancer prevention, diagnosis and...
Every year, over 2 million women are diagnosed with breast cancer. Although considerable progress was made within the last years in cancer prevention, diagnosis and treatment, breast cancer is still responsible for over 600,000 of deaths per year. Over the years, numerous mouse models have been developed to understand breast cancer etiology and progression. Among those, mammary carcinomas induced by carcinogen, such as 7,12-dimethylbenz[a]anthracene (DMBA), has been widely used. Generally, 30-70% of mice exposed to 4-6 weekly doses of 1mg of DMBA during the peripubertal period (4-10 weeks of age) will develop mammary tumors within 150-200 days after the first exposure, that sometime metastasize to the lungs. As a result, DMBA-induced tumorigenesis is thought to be an accurate and relevant model to study breast cancer as it closely mimics this multistep process. This chapter presents the typical protocol used in mice to induce mammary gland tumors using DMBA. The influence of the number of doses and the total burden of DMBA given, as well as of the age and strain of the mice on mammary gland incident and on tumor onset are discussed. The current knowledge regarding mechanisms involved in DMBA-induced tumorigenesis is also presented.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthracenes; Carcinogenesis; Carcinogens; Mammary Neoplasms, Experimental; Mice
PubMed: 33785167
DOI: 10.1016/bs.mcb.2020.09.003 -
Endocrine Regulations Mar 2001The induction of mammary gland and other organ tumours by selected chemical carcinogens, 1-methyl-1-nitrosourea, 7,12-dimethylbenzanthracene, diethylnitrosoamine and... (Comparative Study)
Comparative Study Review
The induction of mammary gland and other organ tumours by selected chemical carcinogens, 1-methyl-1-nitrosourea, 7,12-dimethylbenzanthracene, diethylnitrosoamine and azoxymethane is described and their application in experimental carcinogenesis research is discussed.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Azoxymethane; Carcinogens; Diethylnitrosamine; Methylnitrosourea; Neoplasms, Experimental
PubMed: 11308997
DOI: No ID Found -
Biotechnic & Histochemistry : Official... Nov 2023We evaluated the effects of prenatal and postnatal dietary zinc (Zn) deficiency or supplementation on mammary gland morphology and on acute response to...
We evaluated the effects of prenatal and postnatal dietary zinc (Zn) deficiency or supplementation on mammary gland morphology and on acute response to 7,12-dimethylbenzanthracene (DMBA) in pubertal female rats. On gestational day 10 (GD 10), rat dams were allocated randomly into three experimental groups of 10: a Zn-adequate diet group (ZnA) fed 35 mg Zn/kg chow, a Zn-deficient diet group (ZnD) fed 3 mg ZN/kg chow and a Zn-supplemented diet group (ZnS) fed 180 mg Zn/kg chow. After weaning, female offspring were fed the same diet as their dams until postnatal day 53 (PND 53). All animals received a single 50 mg/kg dose of DMBA on PND 51 and were euthanized on PND 53. Female ZnD offspring exhibited significantly less weight gain compared to the ZnA group and reduced mammary gland development compared to the ZnD and ZnA groups. By PND 53, the Ki-67 labeling index in mammary gland epithelial cells was significantly greater for the ZnS group than for the ZnA and ZnD groups. Apoptosis and ER-α indices did not differ among groups. The ZnD group exhibited significantly increased lipid hydroperoxide (LOOH) levels and decreased catalase and glutathione peroxidase (GSH-Px) activity compared to the ZnA and ZnS groups. The ZnS group exhibited significantly reduced superoxide dismutase (SOD) activity compared to the ZnA and ZnS groups. We observed atypical ductal hyperplasia in the mammary gland of female ZnS group offspring compared to the ZnA and ZnD groups and decreased expression of the and genes related to apoptosis inhibition and DNA damage repair, respectively. Both the Zn-deficient and Zn-supplemented diet exerted adverse effects on offspring mammary gland morphology and acute response to DMBA.
Topics: Pregnancy; Rats; Female; Animals; 9,10-Dimethyl-1,2-benzanthracene; Diet; Apoptosis; Zinc
PubMed: 37022146
DOI: 10.1080/10520295.2023.2196092 -
Cancer Letters Jul 19942,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds inhibit diverse estrogen-induced responses in the rodent uterus and human breast cancer cells. The...
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds inhibit diverse estrogen-induced responses in the rodent uterus and human breast cancer cells. The effects of a single non-toxic dose of TCDD (10 micrograms/kg) on the development of mammary tumors was investigated in female Sprague-Dawley rats treated with an oral dose of 7,12-dimethylbenzanthracene (DMBA) (20 mg). In rats which developed mammary tumors, subsequent treatment with corn oil (vehicle) resulted in a 3.9-fold increase in mammary tumor volume after 21 days. In contrast, a second group of rats with mammary tumors were treated with a non-toxic dose of TCDD (10 micrograms/kg) and after 21 days, the mean tumor volumes decreased from 89.7 +/- 53 mm3 to 24.9 +/- 28.5 mm3. Moreover, these results demonstrate the antitumorigenic activity of TCDD in female Sprague-Dawley rats.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Female; Mammary Neoplasms, Experimental; Polychlorinated Dibenzodioxins; Rats; Rats, Sprague-Dawley
PubMed: 8033067
DOI: 10.1016/0304-3835(94)90144-9 -
The Journal of Toxicological Sciences May 1995Radiosensitization of mice by dimethylbenzanthracene, diphenylcyclopropenone and aminoanthraquinones was investigated in a model where survival time after lethal...
Radiosensitization of mice by dimethylbenzanthracene, diphenylcyclopropenone and aminoanthraquinones was investigated in a model where survival time after lethal radiation was scored. Survival time was shortened by nontoxic doses of the chemicals. The used in vivo system confirmed the radiosensitizing potential of dimethylbenzanthracene reported previously with in vitro studies. Moreover, radiosensitizing properties of diphenylcyclopropenone and aminoanthraquinones could be demonstrated. The sensitizing interaction of these chemicals with radiation adds a new facet to their toxicological spectrum and could, by enhancing radiation effects, influence estimates of risk. On the other hand, diphenylcyclopropenone or aminoanthraquinones deserve consideration as topical sensitizers in conditions where radiation is indicated to treat cutaneous malignancies.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anthraquinones; Cyclopropanes; Female; Gamma Rays; Mice; Mice, Inbred C3H; Radiation Injuries, Experimental; Radiation-Sensitizing Agents; Survival Rate
PubMed: 7473893
DOI: 10.2131/jts.20.149 -
Environmental Health Perspectives Jun 2009Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.
BACKGROUND
Bisphenol A (BPA) is widely used in the manufacture of polycarbonate plastics, including infant formula bottles.
OBJECTIVES
Based on the reported endocrine disruptor activity of this polyphenol, we hypothesized that exposure to BPA early in life would elicit developmental changes in the mammary tissue and cause a predisposition for mammary cancer.
METHODS
We exposed neonatal/prepubertal rats to BPA via lactation from nursing dams treated orally with 0, 25, and 250 mug BPA/kg body weight/day. For tumorigenesis studies, female offspring were exposed to 30 mg dimethylbenzanthracene (DMBA)/kg body weight at 50 days of age.
RESULTS
The combination of DMBA treatment with lactational exposure to BPA demonstrated a dose-dependent increase in mammary tumor multiplicity and reduced tumor latency compared with controls. In the absence of DMBA treatment, lactational BPA exposure resulted in increased cell proliferation and decreased apoptosis at 50 but not 21 days postpartum (shortly after last BPA treatment). Using Western blot analysis, we determined that steroid receptor coactivators (SRCs) 1-3, Akt, phosphorylated Akt, progesterone receptor A (PR-A), and erbB3 proteins were significantly up-regulated at 50 days of age.
CONCLUSIONS
The data presented here provide the first evidence that maternal exposure to BPA during lactation increases mammary carcinogenesis in a DMBA-induced model of rodent mammary cancer. Changes in PR-A, SRC 1-3, erbB3, and Akt activity are consistent with increased cell proliferation and decreased apoptosis playing a role in mammary cancer susceptibility. These alterations provide an explanation of enhanced mammary carcinogenesis after lactational BPA exposure.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benzhydryl Compounds; Carcinogens; Female; Lactation; Mammary Glands, Animal; Mammary Neoplasms, Animal; Maternal Exposure; Phenols; Rats; Rats, Sprague-Dawley
PubMed: 19590682
DOI: 10.1289/ehp.11751