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Methods in Cell Biology 2021Mouse models of cancer are essential in furthering our understanding both of the mechanisms that drive tumor development and the immune response that develops in...
Mouse models of cancer are essential in furthering our understanding both of the mechanisms that drive tumor development and the immune response that develops in parallel, and also in providing a platform for testing novel anti-cancer therapies. The majority of solid tumor models available rely on the injection of existing cancer cell lines into naïve hosts which, while providing quick and reproducible model systems, typically lack the development of a tumor microenvironment that recapitulates those seen in human cancers. Administration of the carcinogen 3-methylcholanthrene (MCA), allows tumors to develop in situ, forming a tumor microenvironment with an established stroma and vasculature. This article provides a detailed set of protocols for the administration of MCA into mice and the subsequent monitoring of tumors. Protocols are also provided for some of the routinely used downstream applications that can be used for MCA tumors.
Topics: Animals; Disease Models, Animal; Fibrosarcoma; Immunity; Methylcholanthrene; Mice; Tumor Microenvironment
PubMed: 33785169
DOI: 10.1016/bs.mcb.2020.09.007 -
Chemico-biological Interactions Oct 2018Glutathione S-transferases (GSTs), the versatile phase II biotransformation enzymes, metabolize and detoxify a wide variety of toxic chemical compounds like carcinogens,... (Review)
Review
Glutathione S-transferases (GSTs), the versatile phase II biotransformation enzymes, metabolize and detoxify a wide variety of toxic chemical compounds like carcinogens, chemotherapeutic drugs, environmental pollutants and oxidative stress products. GSTs are currently of great interest in drug discovery, nanotechnology and biotechnology because of their involvement in many major cellular processes. GSTs, which are either homo or hetero dimeric proteins mediate catalytic binding between glutathione (GSH) and an array of either endogenous or exogenous toxic compounds to form a highly soluble detoxified complex which is then eliminated. Polycyclic aromatic hydrocarbons (PAHs) which are composed of two or more benzene rings bonded as linear, cluster or angular arrangements are used as intermediaries in pharmaceuticals, agricultural products, photographic products, thermosetting plastics, lubricating materials and other chemical products. Foods those cooked at high temperatures by grilling, roasting, frying and smoking are the main sources for the persistent bio-accumulation of PAHs in food chain. The carcinogenic, mutagenic and immunosuppressive effects of PAHs are well established. A well-known polycyclic aromatic hydrocarbon, methylcholanthrene is a potential carcinogenic, neurotoxic, mutagenic and tumour causing agent that is used as an experimental carcinogen in biological research. Methylcholanthrene converts into reactive metabolites when it enters living cells and those reactive metabolites oxidize DNA, RNA, proteins and lipids and form DNA and protein adducts as well. GSTs play major role in the detoxification of reactive metabolites of methylcholanthrene by mediating catalytic binding with GSH to form a highly soluble detoxified complex which is then eliminated. This review summarizes the role of GSTs in the detoxification of a polycyclic aromatic hydrocarbon, methylcholanthrene.
Topics: Animals; Brain; Glutathione Transferase; Humans; Inactivation, Metabolic; Methylcholanthrene; Polycyclic Aromatic Hydrocarbons
PubMed: 30145136
DOI: 10.1016/j.cbi.2018.08.023 -
International Journal of Molecular... Mar 20233-methylcholanthrene (3-MC) is a highly toxic environmental pollutant that impairs animal health. 3-MC exposure can cause abnormal spermatogenesis and ovarian...
3-methylcholanthrene (3-MC) is a highly toxic environmental pollutant that impairs animal health. 3-MC exposure can cause abnormal spermatogenesis and ovarian dysfunction. However, the effects of 3-MC exposure on oocyte maturation and embryo development remain unclear. This study revealed the toxic effects of 3-MC exposure on oocyte maturation and embryo development. 3-MC with different concentrations of 0, 25, 50, and 100 μM was applied for in vitro maturation of porcine oocytes. The results showed that 100 μM 3-MC significantly inhibited cumulus expansion and the first polar body extrusion. The rates of cleavage and blastocyst of embryos derived from 3-MC-exposed oocytes were significantly lower than those in the control group. Additionally, the rates of spindle abnormalities and chromosomal misalignments were higher than those in the control group. Furthermore, 3-MC exposure not only decreased the levels of mitochondria, cortical granules (CGs), and acetylated α-Tubulin, but also increased the levels of reactive oxygen species (ROS), DNA damage, and apoptosis. The expression of cumulus expansion and apoptosis-related genes was abnormal in 3-MC-exposed oocytes. In conclusion, 3-MC exposure disrupted the nuclear and cytoplasmic maturation of porcine oocytes through oxidative stress.
Topics: Animals; Swine; Methylcholanthrene; Oogenesis; Oocytes; Oxidative Stress; Reactive Oxygen Species; Embryonic Development; In Vitro Oocyte Maturation Techniques
PubMed: 36982641
DOI: 10.3390/ijms24065567 -
Journal of the National Cancer Institute Jun 1957
Topics: Methylcholanthrene; Neoplasms; Sarcoma
PubMed: 13502695
DOI: No ID Found -
Chemosphere Jan 20223-methylcholanthrene (3 MC) is an environmental compound belonging to the PAHs and is reportedly thought to be a risk factor for the prevalence of hepatic function...
3-methylcholanthrene (3 MC) is an environmental compound belonging to the PAHs and is reportedly thought to be a risk factor for the prevalence of hepatic function disorder. Here, a dose of 0.5 mg/kg of 3 MC was given to 4-week-old male and female mice (F0) in their diet for 6 weeks. After exposure, then the mice were mated between different groups. The first filial (F1) generation offspring of exposed or unexposed parental mice were sacrificed at the age of 5 weeks (F1-5 W), and the potential effects on the F0 and F1 offspring were evaluated. The results showed that the total bile acids (TBAs) in the serum and feces in F0 females and female F1-5 W individuals born from female mice exposed to 3 MC decreased, while the TBAs in the liver increased. The transcriptional levels of major genes participating in synthesis, regulation, transportation and apical uptake was also altered correspondingly. In addition, the transcription of some genes related to inflammation was enhanced in these mice. Further investigation revealed that in addition to distinct changes in the mucus secretion, tight junction proteins and ion transport were induced, and antimicrobial peptides were also disrupted in the intestine of F0 mice and F1-5 W female offspring of maternal mice exposed to 3 MC. Our results suggested that exposure to 3 MC, but not male exposure, had the potential to interfere with BAs metabolism, affecting gut barrier function. Females were more seriously affected than males.
Topics: Animals; Bile Acids and Salts; Enterohepatic Circulation; Female; Liver; Male; Methylcholanthrene; Mice; Reproduction
PubMed: 34346331
DOI: 10.1016/j.chemosphere.2021.131681 -
The Biochemical Journal Jan 19661. A chromatographic investigation of the products of the metabolism of 3-methylcholanthrene by rat-liver homogenates showed the formation of compounds with the...
1. A chromatographic investigation of the products of the metabolism of 3-methylcholanthrene by rat-liver homogenates showed the formation of compounds with the properties of 1- and 2-hydroxy-3-methylcholanthrene, cis- and trans-1,2-dihydroxy-3-methylcholanthrene and 11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene. A glutathione conjugate that is probably S-(11,12-dihydro-12-hydroxy-3-methyl-11-cholanthrenyl)glutathione was also detected. 3-Methylcholanthrene-1- and -2-one and -1,2-quinone were also present, but these products may have arisen by the chemical oxidation of the corresponding hydroxy compounds. 2. Other metabolic products were tentatively identified as 9- and 10-hydroxy-3-methylcholanthrene, 4,5-dihydro-4,5-dihydroxy-3-methylcholanthrene and 3-hydroxymethylcholanthrene. 3. 1- and 2-Hydroxy-3-methylcholanthrene were converted by homogenates into the related ketones and into products with the properties of cis- and trans-1,2-dihydroxy-3-methylcholanthrene: 3-methylcholanthren-1- and -2-one were converted into their related hydroxy compounds and into the isomeric 1,2-dihydroxy compounds. The isomeric 1,2-dihydroxy compounds were each partly converted into the other isomer by these homogenates. All the above substrates also yielded products that appeared to be derivatives of 3-hydroxymethylcholanthrene. 4. 3-Methylcholanthrylene was converted by rat-liver homogenates into products with the properties of trans-1,2-dihydroxy-3-methylcholanthrene, 2-hydroxy-3-methylcholanthrene and 3-methylcholanthren-2-one. A small amount of the cis-1,2-dihydroxy compound was also formed, together with a glutathione conjugate that is possibly S-(2-hydroxy-3-methyl-1-cholanthrenyl)glutathione or its positional isomer. 5. An unidentified product was detected in the metabolism of 3-methylcholanthrene, the monohydroxy compounds, the ketones and the dihydroxy compounds, the formation of which appeared to involve metabolism at the 1,2-bond. 6. 11,12-Epoxy-11,12-dihydro-3-methylcholanthrene was converted by rat-liver homogenates into products with the properties of 11-hydroxy-3-methylcholanthrene (or, less likely, the 12-isomer), 11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene and the glutathione conjugate described above. Products with the properties of these compounds were formed when the epoxide was allowed to react with glutathione in an aqueous medium. 7. Mouse-liver homogenate converted 3-methylcholanthrene into products with the chromatographic properties of 1- and 2-hydroxy-3-methylcholanthrene, cis- and trans-1,2-dihydroxy-3-methylcholanthrene, 11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene, 3-methylcholanthrene-1- and -2-one and -1,2-quinone and the unidentified hydroxy-3-methylcholanthrenes. 8. The syntheses of cis- and trans-1,2-dihydroxy-3-methylcholanthrene, 3-methylcholanthren-2-one, 2-hydroxy-3-methylcholanthrene, 3-methylcholanthrylene, 11,12-epoxy-11,12-dihydro-3-methylcholanthrene and trans-11,12-dihydro-11,12-dihydroxy-3-methylcholanthrene are described.
Topics: Animals; Chemistry Techniques, Analytical; Chromatography, Thin Layer; In Vitro Techniques; Liver; Methylcholanthrene; Rats; Subcellular Fractions
PubMed: 5938646
DOI: 10.1042/bj0980215 -
Bratislavske Lekarske Listy 2020Skin is the body's first defence against direct exposure to variety of chemicals. Polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (3-MC) are common in...
BACKGROUND
Skin is the body's first defence against direct exposure to variety of chemicals. Polycyclic aromatic hydrocarbons such as 3-methylcholanthrene (3-MC) are common in polluted urban air and have a potential of producing harmful effects. Moreover, their late effects can occur months or years after exposure.
OBJECTIVES
We aimed to investigate the long-term effects of 3-MC induced dermal toxicity on the expression of markers of apoptosis, pleiotropic cytokines, and oxidative stress and to determine the protective effect of cisplatin.
METHODS
Groups were designed as control (group 1), 3-MC applied (group 2) and 3-MC+cisplatin applied mice (group 3). Cutaneous expressions of TGFβ, PDGFA, PDGFC, bFGF, PDGFRα, USP28, and Ki67 were evaluated with qPCR. Total oxidant (TOS), total antioxidant (TAS) and oxidative stress index (OSI) values were determined in liver and kidney tissues.
RESULTS
The expression levels of TGFβ, PDGFRα, USP-28, Ki67, and PDGFA were decreased significantly in MC applied groups. Renal TAS levels were significantly lower in group-3. Liver and kidney OSI values were increased in both groups 2 and 3.
CONCLUSION
The results indicated that low dose 3-MC caused oxidative stress and downregulated apoptotic and cytokine markers in the long term and cisplatin had no ameliorative effects on this degeneration processes (Tab. 3, Fig. 3, Ref. 32). Text in PDF www.elis.sk.
Topics: Animals; Antioxidants; Biomarkers; DNA Damage; Methylcholanthrene; Mice; Oxidative Stress
PubMed: 32356428
DOI: No ID Found -
The Journal of Experimental Medicine Jan 1958The repeated administration of 3-methylcholanthrene to adolescent rats resulted in (a) a profound, incomplete, and selective depression of certain hypophyseal functions;...
The repeated administration of 3-methylcholanthrene to adolescent rats resulted in (a) a profound, incomplete, and selective depression of certain hypophyseal functions; (b) decreased growth of transplanted mammary tumors; and (c) a retardation of body growth. Only the last mentioned effect was reversed by forced feeding. The retarded rate of body growth induced by 3-methylcholanthrene was prevented by the concurrent administration of dihydrotestosterone or progesterone, or by ovariectomy; rats so treated became overweight despite the injection of 3-methylcholanthrene. Phenolic estrogens intensified the retardation of body growth induced by 3-methylcholanthrene and emaciation resulted. The administration of 3-methylcholanthrene resulted in decreased gonadotrophin production by the pituitary and the ovaries were more drastically affected by the depression of pituitary activity than the adrenals were. The compound exerted differential effects on the pituitary glands of males and females respectively. Hormonal functions of both ovary and testis were decreased in rats treated with 3-methylcholanthrene but, whilst ovarian weight was much reduced, the size of the testis was not decreased and the germinal epithelium of the male was little affected by the treatment in most instances. There was a considerable reduction of the content of alkaline phosphatase in the breast of intact rats treated with 3-methylcholanthrene but atrophy of the mammary epithelium did not occur and hyperplasia of the mammary tree was often observed. The administration of 3-methylcholanthrene considerably slowed the growth of transplanted mammary tumors characterized by high dependence on hormones and the concurrent administration of gonadotrophin restored the growth rate of the tumors. The administration of 3-methylcholanthrene or androstan-17beta-ol-3-one was only moderately effective in controlling the growth of transplanted mammary tumors characterized by low hormonal dependence; the combined administration of these compounds was highly efficacious in retarding the growth of these refractory tumors. 3-Methylcholanthrene partially retarded the growth of mammary fibroadenomas in hypophysectomized rats.
Topics: Animals; Endocrine Glands; Endocrine System; Estrogens; Female; Humans; Male; Mammary Neoplasms, Animal; Mammary Neoplasms, Experimental; Metabolism; Methylcholanthrene; Neoplasms, Experimental; Ovariectomy; Pharmaceutical Preparations; Rats
PubMed: 13481252
DOI: 10.1084/jem.107.1.13 -
British Journal of Cancer Aug 1975The uptake of 3-methycholanthrene and its metabolism to water-soluble derivatives were both determined in organ cultures of mouse and rat tissues, including prostate,...
The uptake of 3-methycholanthrene and its metabolism to water-soluble derivatives were both determined in organ cultures of mouse and rat tissues, including prostate, skin, lung and skeletal muscle. All the tissues concentrated the carcinogen from the medium and metabolized part of it to water-soluble compounds. The uptake of tritiated 3-methylcholanthrene was highest in the absence of serum and declined with rising serum concentration. Except for skeletal muscle, it was consistently higher in the murine tissues. The uptake of the hydrocarbon by rat and mouse prostates rose rapidly with time, reaching a maximum after 18 h incubation; the amounts of carcinogen in the tissue then declined and remained at a lower level for the rest of the observation period. The major part of the radioactivity was released within 5 h of transferring the explants to medium without the tracer; 25-40% of the peak concentration of carcinogen, however, still remained in the tissue and further medium changes could not remove any more. Addition of unlabelled 3-methylcholanthrene to the initial incubation increased the radioactivity taken up and caused substantially larger quantities of the carcinogen to be retained after the medium had been changed. The explants converted between 15% and 30% of the 3-methylcholanthrene which they had incorporated to water-soluble derivatives within 48 h but there was no obvious relationship between the amounts of hydrocarbon taken up by the different tissues and the proportions metabolized. A considerable part of the 3-methylcholanthrene in the explants remained unconverted 24 h after its removal from the medium.
Topics: Animals; Lung; Male; Methylcholanthrene; Mice; Mice, Inbred C3H; Muscles; Organ Culture Techniques; Prostate; Rats; Skin; Solubility; Time Factors; Water
PubMed: 1240005
DOI: 10.1038/bjc.1975.152 -
Science (New York, N.Y.) Sep 1952
Topics: Carcinogenesis; Hypophysectomy; Methylcholanthrene; Pituitary Gland
PubMed: 12984119
DOI: 10.1126/science.116.3013.331