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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DNA synthesis in a transplanted hepatoma induced by 3'-methyl-4-dimethylaminoazobenzene was significantly reduced (P less than 0.01) in rats maintained on diets low (0.4 mug/g) or high (greater than or equal to 500 mug/g) in zinc when compared with control animals given 60 mug zinc/g. 3-Methylcholanthrene-induced carcinogenesis was considerably lowered in mice receiving the same low or high zinc diets during the induction periods.
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PMID:Zinc intake, neoplastic DNA synthesis, and chemical carcinogenesis in rats and mice. 16 62

The effects of Azathioprine (AZA) on the carcinogenesis with 3-Methylcholanthrene (MC) are described. When AZA is given before MC, there is a shortened tumor latency period. When AZA treatment followed MC injection a lengthened latency period was observed. When AZA treatment is given both before and after MC injection, intermediate results were observed. It is concluded that the action of AZA treatment on tumor development depends on the time relationship between this treatment and the injection of the carcinogen. In particular, it is suggested that to obtain an enhancing effect on tumor development, probably by immunosuppression, AZA must be effective at the time or shortly after administration of the carcinogen. When AZA is administered later, an inhibition of tumor development, probably a cytostatic effect becomes prominent.
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PMID:Immunosuppression and Carcinogenesis: effects of azathioprine on induction of sarcomas by 3-methylcholanthrene. 86 43

The placement of cotton thread impregnated with beeswax containing methylcholanthrene (MCA, approximately 600 micrograms) inside the canal of the uterine cervix of virgin, adult mice results in the emergence of precancerous and cancerous lesions in the cervical epithelium. Employing this experimental carcinogenesis model system, the present study evaluates the chemopreventive action of selenium on the incidences of precancerous and cancerous lesions in the cervical epithelium. When selenium was administered through drinking water at the dose level of 1 ppm for 1 week before and 12 weeks following carcinogen thread insertion, the cervical carcinoma incidence, as compared to that in control mice (72%), was 37%. This decline in the incidence of carcinoma was significant (p less than 0.05). The incidences of hyperplasia and dysplasia show a decreasing trend with selenium treatment in MCA-thread-inserted animals.
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PMID:Chemopreventive action of selenium on methylcholanthrene-induced carcinogenesis in the uterine cervix of mouse. 149 53

Methylcholanthrene (approximately 300 micrograms) plus beeswax-impregnated thread, when placed inside the canal of the uterine cervix of virgin female adult mice for 30, 60 and 90 days produced cervical tumors in 0.0, 10 and 30% of mice, respectively. Employing this experimental cervical carcinogenesis model system, the present study evaluated the modulatory influence of medroxyprogesterone acetate (MPA) on the incidences of precancerous and cancerous lesions in the cervical epithelium as well as on phase I and phase II drug metabolizing enzymes and acid soluble sulfhydryl level in the liver. Intramuscular administration of MPA (50 micrograms every 5th day) to the carcinogen-thread inserted mice for 30, 60 and 90 days produced cervical tumors respectively in 0.0, 13.3 and 60.5% (P less than 0.05) of mice. A significant increase (P less than 0.05) in hyperplasia was also observed in the present study. A significant decrease in cytochrome b5 was found after 30 days.
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PMID:Modulatory influence of injectable contraceptive steroid medroxyprogesterone acetate on methylcholanthrene-induced carcinogenesis in the uterine cervix of mouse. 153 45

The combined action of 7,12-dimethylbenz[a]anthracene (DMBA) and alpha-naphthoflavone (alpha NF) on the survival and neoplastic transformation of C3H10T1/2 mouse embryo fibroblasts has been examined and correlated with DNA adduct formation and removal. When a 24 h DMBA treatment of asynchronously growing cells was followed for the next 24 h by a treatment with alpha NF + DMBA, both killing and transformation per viable cell were abrogated to a large extent. In some instances, transformation was completely abrogated--i.e. reduced to control frequencies--even at nontoxic concentrations of DMBA, indicating that changes in survival were not the reason for the reduction in transformation. Even at toxic concentrations of DMBA, post-treatment with alpha-NF + DMBA resulted in 10-fold reductions in transformation frequency. 3-Methylcholanthrene (3MC) also reversed DMBA cytotoxicity but with a dependence on 3MC concentration that was qualitatively different from that for alpha NF. The abrogation of cell killing occurred at lower molar ratios of alpha NF:DMBA than the abrogation of transformation; less than or equimolar concentrations resulted in maximal abrogation of killing, but about equal concentrations were required to abrogate transformation. Although the preceding findings suggest that different mechanisms may be involved in these endpoints, taken together they suggest that second treatments make apparent the repair of lesions due to a first treatment with DMBA alone. To test this hypothesis, the formation and removal of DMBA-DNA adducts were measured. Adducts were not removed when the second treatment was growth medium alone, but enhanced removal was observed when second treatments consisted of DMBA alone or DMBA plus one of several other polycyclic aromatic hydrocarbons (PAHs). Relative to killing and neoplastic transformation, these results suggest DMBA induces a repair process that limits its own effectiveness--a process that can be sustained by other PAHs.
Carcinogenesis 1992 Apr
PMID:Abrogation of killing and neoplastic transformation of C3H10T1/2 cells due to 7,12-dimethylbenz[a]anthracene. 157 17

The promotional effect of various polychlorinated biphenyls and phenobarbital on enzyme-altered lesions in the rat liver was quantified within the framework of the two-stage carcinogenesis model of Moolgavkar and colleagues. The experiment analyzed here followed an initiation-promotion protocol in which female Wistar rats were initiated with diethylnitrosamine (DEN) at 10 mg/kg body wt for 10 days followed by a 8-week period of promoter treatment with various cytochrome P450 isoenzyme inducing and noninducing compounds. This analysis included 4-monochlorobiphenyl, 2,2',4,5'-tetrachlorobiphenyl, 3,3',4,4'-tetrachlorobiphenyl and 3-methylcholanthrene, all administered at 150 mumol/kg body wt, and phenobarbital which was administered continuously in the diet at 0.05% until termination. Animals were killed either 1 or 9 weeks after the end of treatment and their livers were examined for enzyme histological alterations. Focal transections were classified as falling into three phenotypic categories: ATPase dominant, GGT dominant, or ATPase plus GGT (coextensive). A quantitative method was used to analyze the data consisting of the number and sizes of the focal transections. The number of cells altered by the DEN treatment and cell kinetic parameters measuring the promotional effect of the various compounds were estimated. On the basis of these estimates, we computed the number of nonextinct altered foci and their volume fraction as functions of time. We found that foci exhibiting the coextensive phenotype respond most efficiently to promoter treatment, while GGT dominant foci respond weakly to all the promoters with the exception of 3-MC. For phenobarbital, we observed a significant slowing of focal cell proliferation over time.
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PMID:Effects of polychlorinated biphenyls in rat liver: quantitative analysis of enzyme-altered foci. 168 71

The role of transforming growth factor-beta 1 (TGF-beta 1) in multisage carcinogenesis in mouse skin was assessed by studying its growth inhibitory effects on nontumorigenic and tumorigenic keratinocytes and by examining its mRNA expression in vitro and during epidermal hyperproliferation and multistage carcinogenesis. While growth of primary basal keratinocytes was inhibited by TGF-beta 1 in doses as low as 0.1 ng/mL, the immortal keratinocyte line MCA/3D ("putatively initiated" cells) responded to TGF-beta 1 with slightly reduced sensitivity, and the papilloma-producing keratinocyte line 308 was considerably less sensitive. In contrast, the squamous carcinoma cell line Carc B was completely nonresponsive, and two other tumorigenic cell lines (PDV and PDVC57) were sensitive to growth inhibition by TGF-beta 1. Steady-state levels of TGF-beta 1 mRNA were high in all the malignant cell lines and in line 308 papilloma cells, but low in primary basal cells and in the nontumorigenic keratinocyte lines V2, Reb1, and MCA/3D. Our in vivo studies showed that tumor promoters, but not mitogenic or weak hyperplasiogenic agents, were able to induce transient expression of TGF-beta 1 mRNA in mouse epidermis. A constitutive overexpression of TGF-beta 1 mRNA was observed in malignant carcinomas but not in the benign premalignant lesions, indicating that overexpression may be associated with malignant progression.
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PMID:TGF-beta 1 and skin carcinogenesis: antiproliferative effect in vitro and TGF-beta 1 mRNA expression during epidermal hyperproliferation and multistage tumorigenesis. 171 Apr 62

Normally the expression of the murine type I keratin K13 is restricted to differentiating cells of internal squamous epithelia which line the oral cavity and the upper digestive tract. Recently, however, we were able to show that K13 is aberrantly but constitutively expressed without its normal type II partner K4 also in differentiating parts of 7,12-dimethylbenz(a)anthracene (DMBA/TPA) 12-O-tetradecanoylphorbol-13-acetate-induced squamous cell carcinomas of mouse back skin, whereas its likewise suprabasal expression in papillomas is variable (Nischt et al., Mol. Carcinogenesis 1, 96-108, 1988). In an attempt to reproduce the aberrant expression of K13 in a mouse in vitro system, we have investigated eight established murine epidermal cell lines for their putative ability to express K13. The cell lines differed distinctly in their derivation and comprised cell lines originating from DMBA/TPA induced papillomas (line SP1) or DMBA-treated adult mouse epidermis (line 308) as well as cell lines derived from DMBA or DMBA/TPA-treated primary epidermal keratinocytes (lines PDV and MCA 3D) and cell lines which arose spontaneously by long-term culture of normal epidermal keratinocytes (lines HEL 30 degrees HEL 37 degrees, HELP I and HELP III). We show that, independent of their derivation, all cell lines possess the intrinsic property to aberrantly express K13. Invariably the K13 gene is not expressed when the lines are cultured under low Ca2+ conditions (0.05 mM) and thus prevented from differentiation. Its expression can, however, be induced either by increasing the extracellular Ca2+ concentration or by the addition of physiological concentrations of vitamin A acid to low Ca2+ medium. Whereas in the latter case, K13 expression occurs without concomitant induction of morphological differentiation of the cells, Ca2+ elevation in the culture medium induces squamous differentiation and K13 expression occurs only in differentiating cells, thus reflecting the situation observed in in vivo tumors. All cell lines exhibit a concentration optimum for the stimulatory agents; however, the degree of maximal K13 expression varies considerably among the individual cell lines and shows a striking correlation with the reported tumorigenicity of the lines after transplantation to animals. In contrast, a tentatively suggested correlation between the activation of the Ha-ras gene and the aberrant expression of K13 (Nischt et al., Mol. Carcinogenesis 1, 96-108, 1988) could not definitely be confirmed since we observed K13 expression also in three cell lines which did not carry a mutation in codon 61 of the Ha-ras gene.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Aberrant in vitro expression of keratin K13 induced by Ca2+ and vitamin A acid in mouse epidermal cell lines. 171 71

The soybean-derived Bowman-Birk inhibitor (BBI) has been shown to inhibit carcinogenesis in both in vitro and in vivo model systems. In the present study, protease enzyme activity in selected tissues of male strain A mice was measured by hydrolysis of the synthetic substrate Boc-Val-Pro-Arg-MCA (t-butoxycarbornylvalylprolylarginine 7-amido-4-methylcoumarin). When added to homogenates of lung, liver and kidney in vitro, purified BBI inhibited hydrolytic activity at concentrations ranging from 10-100 microM. In vivo, hydrolytic activity was found to be significantly and in a dose-dependent manner, decreased in the lung as early as 2 h after i.p. injection of purified BBI. Less inhibition was found in the liver and kidney after in vivo administration of purified BBI. A crude preparation of BBI, given at 100 mg/kg, had no influence on the overall disposition of radiolabeled benzo[alpha]pyrene in mice although it decreased the hepatic activities of cytochrome P-450, 7-ethoxycoumarin-O-deethylase and ethoxy resorufin-O-deethylase. It is concluded that the chemopreventive effects of BBI on mouse lung tumor development are most likely mediated through its protease-inhibitory properties in the target organ rather than by a non-specific effect on metabolism and disposition of carcinogens.
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PMID:Acute effects of the Bowman-Birk protease inhibitor in mice. 194 45

Protease inhibitors have been shown to be effective suppressors of carcinogenesis in vitro and in vivo. For example, the potato-derived chymotrypsin inhibitor 1 (CI-1) suppresses radiation transformation of C3H/10T1/2 cells in vitro. In the current study, we have investigated the interaction of CI-1 with C3H/10T1/2 cells. At the concentrations examined, CI-1 was non-toxic and had no effect on the doubling time or saturation density of these cells. This compound was taken up by these cells in a time dependent manner. Analysis of CI-1 from treated cells on a chymotrypsin affinity column revealed that active inhibitor was present in the cells. Additionally, CI-1, as well as the soybean derived Bowman-Birk inhibitor and chymostatin, blocked the cleavage of the peptide substrate Suc-Ala-Ala-Pro-Phe-MCA by intact C3H/10T1/2 cells. We have previously demonstrated that this substrate will reduce the transformation yield following treatment of cells with ionizing radiation. Our results suggest that CI-1 may inhibit transformation of C3H/10T1/2 cells in vitro by inhibiting the activity of Suc-Ala-Ala-Pro-Phe-MCA hydrolyzing activity in these cells.
Carcinogenesis 1991 Apr
PMID:The interaction of the potato-derived chymotrypsin inhibitor with C3H/10T1/2 cells. 201 29


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