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

Following 4 weeks of s.c. injections of 1,2-dimethylhydrazine, a carcinogen that produces colon cancer in CF1 mice, an increase in the unidirectional mucosal to serosal flux and net absorption of sodium was observed in the distal colon. This increase in sodium transport was amiloride sensitive. 1,2-Dimethylhydrazine treatment had no effect on sodium transport in the distal colon of DBA/2 mice, a strain which does not develop colonic malignant transformation. Although stimulation of sodium transport has been observed in cultured cell systems exposed to growth factors, similar changes in sodium transport have not previously been demonstrated in an intact epithelium at an early stage of carcinogenesis. The present study in mouse distal colon demonstrates that sodium transport is altered in 1,2-dimethylhydrazine-induced malignant transformation of the large bowel.
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PMID:Sodium transport in a mouse model of colonic carcinogenesis. 362 Nov 59

Both sexes of BALB/c X DBA/2 F1 mice and F344 rats were treated for 1 week with a diet containing 0.02% of hepatocarcinogenic tryptophan pyrolysate component (Trp P-1 or Trp P-2), and changes in the carcinogen activation enzyme activity in various organs were examined comparatively using a mutation test with Salmonella typhimurium TA98 as a tester bacterium. Hepatic enzymes from untreated mice and rats showed a definite catalytic activity for mutagenic activations of Trp P-1 and Trp P-2, whereas the activities of other organs--such as lung, kidney, small intestine and colon--were undetectable or very low. In both mice and rats either the Trp P-1 or Trp P-2 feeding resulted in induction of cytochrome P-450 isozyme(s), which could mediate in the liver but not in other organs the mutagenic activation of the carcinogen itself. As to the sex difference, the induction of the activation enzyme(s) was greater in the female animals than in the males. Species difference in the activity of hepatic enzymes catalyzing the Trp P-1 and Trp P-2 mutageneses was also observed in animals treated with the basal diet; the activity was higher in mice than in the sex-matched rats (Trp P-1, approximately 1.5-fold; Trp P-2, approximately 7-fold). When diet containing Trp P-1 or Trp P-2 was fed for 1 week, the activity of the rat liver for Trp P-1 mutagenesis was of a level similar to that of the sex-matched mice, but for Trp P-2 mutagenesis it was less than half that in the mice. The induced hepatic enzymes in mice and rats were suggested to be 3-methylcholanthrene-inducible cytochrome P-448 isozymes as determined by mutation tests with Trp P-1, Trp P-2 and two other substrates and by immunochemical analyses of rat hepatic cytochrome P-450 using monoclonal antibodies against rat cytochrome P-448 isozymes. These results indicate that a form of cytochrome P-450 responsible for activation of Trp P-1 and Trp P-2 is inducible by dietary treatment of mice or rats with these carcinogens and that the amount of the cytochrome P-450, including resident and induced forms, is related to the species, sex and organ differences in their carcinogenic susceptibility to these chemicals.
Carcinogenesis 1987 Dec
PMID:Species, sex and organ differences in induction of a cytochrome P-450 isozyme responsible for carcinogen activation: effects of dietary hepatocarcinogenic tryptophan pyrolysate components in mice and rats. 367 14

C57BL/6J (B6) and DBA/2J (D2) mice have different susceptibilities to developmental toxicity and transplacental carcinogenesis induced by in utero exposure to polycyclic aromatic hydrocarbons, which has been associated with polycyclic aromatic hydrocarbon metabolism and inducibility at the Ah locus. The distribution of total 3-methylcholanthrene (3-MC)-associated radioactivity in maternal, placental, and fetal tissues of beta-naphthoflavone-pretreated pregnant B6 and D2 mice was determined up to 12 h after p.o. exposure to [6-14C]-3-MC (63 mg/kg, 20 mu Ci) on gestational day 17. 3-MC-associated radioactivity in maternal plasma was not significantly different in the two strains. However, D2 tissue homogenates had consistently higher levels of 3-MC-associated radioactivity, which included both bound and free parent compound and metabolites. Increased metabolism of 3-MC by B6 maternal liver was suggested by the induced levels of aryl hydrocarbon hydroxylase activity in that tissue and by the observation that levels of total radioactivity decreased more rapidly in B6 tissues than in D2 tissues. The D2 fetal lung, the target tissue for 3-MC-induced transplacental carcinogenesis, appeared to accumulate 3-MC-associated radioactivity for a longer period of time than either the D2 fetal liver or the B6 fetal tissues. This study suggests that the genetic differences in fetal susceptibility to the developmental toxicity and transplacental carcinogenesis of 3-MC may be related to the presystemic elimination of the compound from both maternal and fetal tissues.
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PMID:Strain-dependent differences in the metabolism of 3-methylcholanthrene by maternal, placental, and fetal tissues of C57BL/6J and DBA/2J mice. 375 14

Mouse skin melanomas were induced in two stage skin carcinogenesis with 7,12-dimethylbenz[a]anthracene as initiator and croton oil as promoter. After approximately 25 weeks of promotion, small black macules of the skin were observed in C57BL, CDF1 and BDF1 mice, and progressively grew with time. Macules less than 2 mm in diameter were localized mostly in the lower portion of the dermis and, histologically, these lesions were consistent with the diagnosis of melanocytoma and were composed of polygonal to round cells loaded with large numbers of melanin granules. The cells were closely packed forming well-demarcated cell-nests with occasional columnar arrangement. In the macules over 2 mm in diameter, the cells were closely packed to form irregularly bordered cell-nests, showing invasive growth into the surrounding tissues. The lesions were diagnosed as malignant melanomas. The incidence of benign and/or malignant melanoma differed among strains: 80% in BDF1, 70% in CDF1, 30% in C57BL/6 and 0% in DBA/2 mice. One example of tumor induced in a CDF1 mouse was transplantable to homologous CDF1 mice.
Carcinogenesis 1985 Jun
PMID:Mouse skin melanoma induced in two stage chemical carcinogenesis with 7,12-dimethylbenz[a]anthracene and croton oil. 392 35

The most important target in pharmaceutical therapy against cancer is complete suppression of metastases and recurrence after curative surgical operation. It is fundamentally, a growth inhibition and regression of small number of autochthonous tumors scattering in the host, and coexistence between tumor and host is also important. As immunosuppressive anticancer drugs have detrimental effects for patients in such cases, application of strong immunopotentiators such as lentinan should be expected. Lentinan showed a prominent effect on suppression of metastases in experimental systems of clinical models using MH-134 hepatoma, Madison-109 lung carcinoma and DBA/2.MC.CS-1 fibrosarcoma. Suppression of carcinogenesis may be considered as one of experimental methods to prevent metastases in a viewpoint of regression of small number of autochthonous tumor cells. Lentinan given at suitable timing and schedule showed marked prophylactic effect on chemical and viral carcinogenesis. Mode of action of lentinan as T-oriented adjuvant in its antitumor and metastases-inhibitory effects is also discussed. Considering excellent end-point results of Phase III with advanced and recurrent gastrointestinal cancer, lentinan is the most hopeful substance to prevent micrometastases.
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PMID:[Experimental studies on growth inhibition and regression of cancer metastases]. 400 87

Chloracne is a follicular hyperkeratosis produced by exposure to certain halogenated aromatic compounds. The rabbit ear bioassay has been used successfully for testing the acnegenic activity of compounds, but the lack of reference data in this species limits its usefulness in correlating chloracne to other toxic effects such as skin carcinogenesis. In this study, a prototype chloracnegen, 3,4,3',4'-tetrachloroazoxybenzene (TCAOB), was used. Five strains of mice (hairless, rhino, rhino+, DBA/2J, and C57BL/6) were treated topically with 100 microliters of 0.001, 0.01, or 0.1% TCAOB daily for 3-9 wk. Skin and liver histology were performed and hepatic enzyme activities measured. At the 0.001% TCAOB level, induction of hepatic aniline hydroxylase and cytochrome P-450 occurred in the C57BL/6 mice and induction of cytochrome c reductase occurred in the rhino mice. Dose-dependent gross and histologic skin lesions, characteristic of follicular hyperkeratosis, were observed in the rhino and hairless strains at the 0.01% and 0.1% levels. These two strains also had induction of hepatic cytochrome c reductase, cytochrome P-450, and aniline hydroxylase at TCAOB concentrations of 0.01 or 0.1%. These results suggest that the rhino and hairless strains of mice may be useful in the study of chloracne.
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PMID:Assessment of the chloracnegenic response induced by 3,4,3',4'-tetrachloroazoxybenzene in mice. 400 34

The role of metabolic activation of carcinogens in fetal tissue as a determinant of sensitivity in transplacental carcinogenesis was investigated in a pharmacogenetic experiment utilizing backcrosses of C57BL/6 (AhbAhb, responsive to induction of aromatic hydrocarbon metabolism) and DBA/2 (AhdAhd, non-responsive) mice. Responsive (C57BL/6 X DBA/2)F1 and non-responsive DBA mothers, all carrying both responsive (AhbAhd) and non-responsive (AhdAhd) fetuses, were given i.p. doses of the carcinogen 3-methylcholanthrene (MC) ranging from 5 to 175 mg/kg on gestation day 17. At 10 months of age the metabolic phenotype of each offspring was determined, and correlated with number of lung and liver tumors. Both male and female AhbAhd (responsive) offspring in most dose groups presented a consistent two- to three-fold higher incidence of lung tumors than did non-responsive AhdAhd littermates. The difference held for offspring of both (C57BL/6 X DBA)F1 and DBA mothers and it was of statistical significance for one or both sexes at most dosage levels. Hepatocellular tumors were also significantly more frequent in responsive male AhbAhd progeny of (C57BL/6 X DBA/2)F1 mothers than in non-responsive AhdAhd littermates. Progeny of the DBA mothers exhibited significantly more liver and lung tumors than did those of the (C57BL/6 X DBA/2)F1 mothers receiving the same dose. These results suggest that in this model system both maternal and fetal genotype for responsiveness to induction of aromatic hydrocarbon metabolism are important factors modulating fetal carcinogenic risk.
Carcinogenesis 1985 Sep
PMID:Fetal mouse susceptibility to transplacental lung and liver carcinogenesis by 3-methylcholanthrene: positive correlation with responsiveness to inducers of aromatic hydrocarbon metabolism. 402 36

Various treatment protocols were used to investigate the time-dependent decrease in sister chromatid exchanges (SCEs) in bone marrow cells following treatment of C57Bl/6J X DBA/2J F1 (DB2F1) mice by i.p. injection of cyclophosphamide (15 mg/kg). The major factor in the time-related decrease in SCE-inducing lesions is the considerable cytotoxicity or selection of less highly damaged cells over successive cyclophosphamide post-treatment cycles. A constant rate of selection of 0.61 and 0.65%, respectively, was apparent over post-treatment cycles 1-2 and 2-3. In addition, second- and third-division SCE data produced by various protocols indicate persistence of a fraction of cyclophosphamide's SCE-inducing lesions for at least three post-treatment cycles. Comparison of the persistence of cyclophosphamide's SCE-inducing lesions with our previously reported data for diepoxybutane and ethyl carbamate reveals that the rate of repair of SCE-inducing lesions is inversely related to tumorigenic activities.
Carcinogenesis 1985 Aug
PMID:Persistence of cyclophosphamide-induced damage in bone marrow as indicated by sister chromatid exchange analysis. 404 Apr 43

We examined the binding pattern of nine lectins to N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic lesions in Syrian hamsters. These lectins were Arachis hypogaea (PNA), Dolichos biflorus (DBA), Griffonia simplicifolia I (GS-I), Helix aspersa (HAA), Helix pomatia (HPA), Sophora japonica (SJA), Ricinus communis I (RCA-I), Triticum vulgaris (WGA) and Ulex europaeus I (UEA-I). All of the lectins reacted in untreated control hamsters to varying intensities with cytoplasmic components of acinar cells. GS-I, HPA, RCA-I and UEA-I bound to the basolateral surface and PNA, HAA and HPA to the luminal surface of these cells. All but GS-I, RCA-I and UEA-I stained the cytoplasm of islet cells diffusely. In untreated control hamsters, some ductal cells bound PNA, HAA and RCA-I, whereas these cells reacted negatively to the remaining six lectins. Ductular cells did not bind any of the nine lectins. Hyperplastic ductal cells in untreated hamsters were reactive with all nine lectins; however the intensity of the reactivity, cellular localization and extent differed for each lectin. In carcinogen-treated hamsters, the binding pattern of the lectins to acinar and islet cells did not differ significantly from that in untreated hamsters, whereas cells of induced ductal and ductular lesions bound each of the lectins in different patterns and intensities. The reaction of UEA-I to induced lesions was most consistent, specific and strong, thereby indicating the presence of L-fucose in glycoproteins produced by altered cells. Although the binding affinity of the lectins to induced hyperplastic lesions differed in both a quantitative and qualitative fashion, all dysplastic and malignant lesions were reactive to each lectin. This result indicates a heterogeneity in the carbohydrate structure of the glycoproteins produced by pancreatic cells during carcinogenicity.
Carcinogenesis 1985 Dec
PMID:Lectin binding affinities of induced pancreatic lesions in the hamster model. 406 53

Technical BHC and the alpha, beta, gamma and delta isomers of BHC are carcinogenic for the liver of mice and rats. Mice given the isomers of BHC developed carcinomas and hyperplastic nodules of the liver as early as 24 weeks. Several strains of mice (dd, ICR-JLC, CL1, DDY, IRC, DBA/Z, C3H/HEN, C57BL/6 were susceptible. Male mice were more susceptible to hepatic carcinogenesis than female mice and they appeared to be more susceptible to alpha-BHC. The incidence of neoplasms of the liver was increased when beta-, gamma-, or delta-BHC were each given together with alpha-BHC. PCB-5 promoted the induction of hepatic neoplasms when administered with beta-BHC. Technical BHC and its isomers are carcinogenic for the liver of male and female Wistar rats. Beta-BHC is carcinogenic for the liver of Osborne-Mendel male rats. Osborne-Mendel rats receiving delta-BHC developed cirrhosis of the liver, portal vein thrombosis, and focal necrosis of the skeletal muscle. Male rats ingesting technical BHC or the beta or delta isomers also had atrophic testes.
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PMID:Carcinogenicity of benzene hexachloride and its isomers. 616 79


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