Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diethyldithiocarbamate (DDTC) injected i.p. inhibits remarkably and in a dose-dependent manner 12-O-tetradecanoylphorbol-13-acetate (TPA)-decreased glutathione (GSH) peroxidase and TPA-induced ornithine decarboxylase (ODC) activities in mouse epidermis in vivo. DDTC is more potent in inhibiting these effects of TPA than 16 other antioxidants, free radical scavengers, thiol-containing compounds, and reduced glutathione (GSH) level-raising agents, even though some of these treatments are applied directly to the TPA-treated skin. DDTC also inhibits the effects of several structurally different tumor promoters and the greater GSH peroxidase and ODC responses produced by repeated TPA treatments. The inhibitory effects of DDTC on TPA-decreased GSH peroxidase and TPA-induced ODC activities are additive with those of Na2SeO3 and D-alpha-tocopherol (vitamin E). Interestingly, DDTC is a more effective inhibitor when it is administered after TPA, suggesting that DDTC may supplement, facilitate, and/or enhance the activity of the natural GSH-dependent detoxifying system protecting the epidermis against the oxidative challenge presumably linked to the tumor-promoting activity of TPA. When tested in the initiation-promotion protocols, DDTC inhibits to the same degree complete tumor promotion by TPA and stage 2 tumor promotion by mezerein, in relation with its identical inhibition of the GSH peroxidase and ODC responses to both TPA and mezerein. Moreover, the inhibition of the first stage tumor-promoting activity of TPA by DDTC may be attributed to its ability to inhibit TPA-induced DNA synthesis, a postulated component of the conversion phase of skin carcinogenesis when TPA is used as a stage 1 tumor promoter.
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PMID:Inhibition of multistage tumor promotion in mouse skin by diethyldithiocarbamate. 282 29

The fetal, normal adult, and malignant squamous epitheliums of the cervix were immunohistochemically examined by the avidin-biotin-peroxidase complex method with monoclonal antibodies for blood group antigens (BGAs) A, B, H, Lewis a, and Lewis b. The results were as follows. 1) ABH antigen compatible with ABO status was found in most normal squamous epithelium of fetal and adult cervix. 2) Compatible ABH and A antigen were abolished in small cell nonkeratinizing squamous cell carcinomas (SNKCs) and large cell nonkeratinizing squamous cell carcinomas (LNKCs), respectively. But no remarkable change in ABH antigen expression was observed in other types of cervical lesions. 3) Precursor H antigen was accumulated in all types of malignant lesions. 4) Incompatible expression of A or B antigen was observed in some cases of LNKCs and keratinizing squamous cell carcinomas. 5) Lewis antigens were abolished to various degrees in malignant lesions of the cervix. The present study showed the change in BGAs expression during carcinogenesis of the cervix, but further investigation is needed to elucidate the interaction between these changes in BGAs and the biological behavior of cancer cells.
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PMID:[Expression of blood group antigens A, B, H, Lewis a, Lewis b, in malignant lesions of the uterine cervix]. 283 74

244 cervical tissue specimens with different diagnoses were stained by peroxidase-anti-peroxidase technique (PAP) for assay of the human papillomavirus (HPV) genus-specific antigen, the first of its kind performed in China. HPV antigen was detected in 41.93% of simple condyloma group, in 35.29% of dysplasia with condyloma and in 27.27% of carcinoma with condyloma. There was no positive in the control, dysplasia or carcinoma groups. The antigen positive nuclei were found in the koilocytes or parakeratosis cells in the upper layers of the epithelium. The severer the condyloma, the higher the positive rate of antigen. In the severe condyloma group, the positive rate was as high as 64.71%. The koilocytes were observed in every HPV antigen positive section. In view of the coexistence and continuous transformation of condyloma, dysplasia and carcinoma in pathomorphology, these results provide an important evidence to the further studies on the relation between HPV infection and carcinogenesis of cancer of uterine cervix.
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PMID:[Human papillomavirus infection and carcinogenesis of cancer of uterine cervix. II. Immunoperoxidase localization of papilloma-virus antigen in tissues of the uterine cervix]. 283 40

gamma-Glutamyltranspeptidase (gamma-GT) is known to be increased in putative pre-neoplastic foci but also in the periportal zone I of rat liver under a variety of circumstances not directly related to carcinogenesis. To be able to distinguish between these two instances gamma-GT was studied by enzyme determination in micro-dissections obtained from the two locations and by both histochemical and immunohistochemical staining in serial sections. Altered hepatic foci and alterations in zone I were produced in three models of hepatocarcinogenesis: initiation by N-nitrosomorpholine and tumor promotion by phenobarbital, continuous administration of 2-acetylaminofluorene and continuous administration of methapyrilene hydrochloride. In micro-dissections gamma-GT activity was similarly increased in focal lesions and in zone I after feeding methapyrilene. Histochemically detectable gamma-GT, stained according to Rutenburg et al. (23), was observed both in zone I and in focal lesions. Focal lesions were also ATPase negative and UDP-glucuronyltransferase positive in all three models. gamma-GT in focal lesions could be selectively detected by immunohistochemical staining using antibodies to the rat kidney enzyme and an indirect peroxidase reaction. These findings suggest immunochemical differences between gamma-GT in focal lesions and in zone I.
Carcinogenesis 1986 Sep
PMID:Immunohistochemical differentiation of gamma-glutamyltranspeptidase in focal lesions and in zone I of rat liver after treatment with chemical carcinogens. 287 97

Reduced glutathione (GSH) is mutagenic in Salmonella in the presence of gamma-glutamyltranspeptidase (GGT), with the highest response obtained in strain TA102. Reduced cysteinylglycine, one of the products of GGT metabolism of GSH, is mutagenic in the absence of GGT. In strain TA102, GSH mutagenesis was dependent on molecular oxygen, enhanced by iron, inhibited by EDTA, desferrioxamine mesylate, mannitol, butylated hydroxyanisole, peroxidase and catalase, but not by superoxide dismutase. Binding of GSH or its GGT-dependent metabolites to DNA in vitro was not detected. This is consistent with a model of an indirect mechanism of mutagenesis, i.e. cleavage of GSH by GGT, followed by facile auto-oxidation of the resulting cysteinylglycine, with the production of free radicals which lead to the (pen)ultimate mutagen, H2O2.
Carcinogenesis 1988 May
PMID:Glutathione mutagenesis in Salmonella typhimurium is a gamma-glutamyltranspeptidase-enhanced process involving active oxygen species. 289 53

The generation of superoxide and hydroxyl radicals is known to be implicated in the hydroxylation of 2'-deoxyguanosine (dG) at the C-8 position and of guanine base residues in DNA. It was also shown previously that in the presence of horseradish peroxidase, hydrogen peroxide and Fe3+ - EDTA complex, diethylstilbestrol (DES) induces single strand breaks in DNA, caused by the production of superoxide anion (O2-) and hydroxyl (OH.) radicals. By means of high-pressure liquid chromatography and electrochemical detection a strong indication is adduced that dG is oxidized to 8-hydroxy-2'-deoxyguanosine during peroxidative in vitro metabolism of DES, which might be at the basis of DES induced cell transformation.
Carcinogenesis 1989 Feb
PMID:Peroxidative in vitro metabolism of diethylstilbestrol induces formation of 8-hydroxy-2'-deoxyguanosine. 291 92

Diethylstilbestrol (DES) and four derivatives, viz. tetrafluoro-DES, 3'-hydroxy-DES, Z,Z-dienestrol and hexestrol, were examined for their abilities to form superoxide radicals and to induce DNA strand breaks in the presence of horseradish peroxidase/hydrogen peroxide metabolism in a cell-free system. Furthermore, the induction of strand breaks by these compounds was tested in Syrian hamster embryo (SHE) cells in vitro. Formation of superoxide radicals could be demonstrated by reduction of nitro blue tetrazolium for DES but not for its derivatives. With isolated superhelical DNA, induction of strand breaks in the presence of Fe3+ was observed for DES, tetrafluoro-DES and 3'-hydroxy-DES, while hexestrol and Z,Z-dienestrol were ineffective. In SHE cells, alkaline elution technique showed that DNA strand breaks were induced by DES and all derivatives tested, although only at cytotoxic concentrations. It is concluded that DES, under conditions of peroxidative metabolism, can give rise to superoxide generation and DNA strand breaks, and that these events may play a role in the process of DES-induced cell transformation.
Carcinogenesis 1986 Aug
PMID:Possible role of oxygen radicals in cell transformation by diethylstilbestrol and related compounds. 301 47

Subclinical flat cervical warts are commonly recognized by means of colposcopy. These warty lesions frequently contain cellular atypia of a varying degree showing all the features of cervical intraepithelial neoplasia (CIN) together with the features of wart virus infection e.g. koilocytosis. Human papillomavirus (HPV) antigens and DNA have been found in these lesions which can be called atypical condylomas. The presence of such markers in lesions regarded as having neoplastic potential implicates HPV in cervical carcinogenesis. We investigated a group of Chinese women in Singapore to see whether this hitherto unstudied group showed HPV markers, in particular, HPV antigens by means of the peroxidase-antiperoxidase (PAP) staining technique. We found that histological warty change and HPV antigens were commoner in early compared with advanced CIN. These results, which are similar to previous studies, suggest that the aetiology of cervical carcinoma is probably no different in Singapore than in the West. They also suggest that HPV infection of the cervix is endemic in non-Western countries as well as in the West and may play a role in cervical carcinogenesis in diverse racial groups.
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PMID:Atypical condylomas of the cervix uteri in Singapore women: a histopathological and immunohistochemical study. 302 Nov 7

Expression of the ras oncogene product p21 (ras p21) in benign and malignant human colonic tissues was studied using the monoclonal antibody RAP-5 and the avidin-biotin-peroxidase technique. Histologically normal colonic mucosa and hyperplastic mucosa adjacent to carcinomas (transitional mucosa) were found, in most cases, to be negative for reactivity with the antibody or showed weak staining of a few epithelial cells. Similar findings were observed in hyperplastic and juvenile polyps. Of the 145 adenomas studied, 47 (32.4%) showed detectable levels of ras p21 expression. RAP-5 immunohistochemical staining was significantly associated with the degree of epithelial dysplasia (P less than 0.01) and the size of adenoma (P less than 0.05), but not with the histological type. Fifty-four of 70 primary adenocarcinomas (77.1%) were reactive with RAP-5 and usually demonstrated a higher percentage of stained cells and more intense cytoplasmic staining than that observed in adenomas. Although metastases often displayed a similar or even higher levels of ras p21 expression compared with the primary carcinomas, in 10 cases one or more metastatic lesions showed lower levels of ras p21. These results suggest that enhanced ras p21 expression may, at times, occur in the early stages of human colon carcinogenesis but are probably not associated with metastatic tumour progression.
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PMID:ras p21 oncoprotein expression in human colonic neoplasia--an immunohistochemical study with monoclonal antibody RAP-5. 304 43

The ways in which dietary polyunsaturated fats and antioxidants affect the balance between activation and detoxification of environmental precarcinogens is discussed, with particular reference to the polycyclic aromatic hydrocarbon benzo(a)pyrene. The structure and composition of membranes and their susceptibility to peroxidation is dependent on the polyunsaturated fatty acid (PUFA) content of the cell and its antioxidant status, both of which are determined to a large degree by dietary intake of these compounds. An increase in the PUFA content of membranes stimulates the oxidation of precarcinogens to reactive intermediates by affecting the configuration and induction of membrane-bound enzymes (e.g., the mixed-function oxidase system and epoxide hydratase); providing increased availability of substrates (hydroperoxides) for peroxidases that cooxidise carcinogens (e.g., prostaglandin synthetase and P-450 peroxidase); and increasing the likelihood of direct activation reactions between peroxyl radicals and precarcinogens. Antioxidants, on the other hand, protect against lipid peroxidation, scavenge oxygen-derived free radicals and reactive carcinogenic species. In addition some synthetic antioxidants exert specific effects on enzymes, which results in increased detoxification and reduced rates of activation. The balance between dietary polyunsaturated fats, antioxidants and the initiation of carcinogenesis is discussed in relation to animal models of chemical carcinogenesis and the epidemiology of human cancer.
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PMID:A role for dietary lipids and antioxidants in the activation of carcinogens. 307 48


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