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

N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, and MVE-2, a maleic anhydride-divinyl ether copolymer, were both effective inhibitors of mammary carcinogenesis induced in Sprague-Dawley rats by N-methyl-N-nitrosourea and of urinary bladder carcinogenesis induced in C57BL/6 x DBA/2F1 mice by N-butyl-N-(4-hydroxybutyl)-nitrosamine. However, combined administration of 4-HPR and MVE-2 was no more effective in cancer inhibition than was either agent alone. Retinoids and maleic anhydridedivinyl ethers may exhibit a mechanistic or metabolic antagonism which precludes an additive or synergistic interaction in inhibiting chemical carcinogenesis.
Carcinogenesis 1982
PMID:Inhibition of mammary and urinary bladder carcinogenesis by a retinoid and a maleic anhydride-divinyl ether copolymer (MVE-2). 621 19

The effects of intraurethral or i.p. administration of a mouse skin tumor promoter phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), on rodent urinary bladder transitional epithelium were studied. TPA, when instilled into the urinary bladder of inbred rats (female Fischer, F344) or mice (C3H, ICR, C57BL X DBA/2 F1) at a dose as low as 0.16 nmol, led to a significant (about 10-fold) increase in bladder ornithine decarboxylase (EC 4.1.1.17) (ODC) activity. Peak ODC activity was observed at about 6 hr, and enzyme activity returned to base levels about 14 hr after intravesical TPA. Administration of TPA i.p. in dimethyl sulfoxide also induced vesical ODC at 4 hr after treatment. The magnitude of vesical ODC induction correlated well with the ability of a series of phorbol esters to promote mouse skin tumor formation (TPA greater than phorbol didecanoate greater than phorbol dibenzoate, and phorbol diacetate or phorbol did not induce bladder ODC activity). Mezerein, a second stage mouse skin tumor promoter, induced urinary bladder ODC as much as TPA did. Increased ODC activity by TPA was the result of an increased amount of ODC protein localized mostly (greater than 60%) in urinary bladder mucosa. Intraurethrally administered TPA induced transitional cell hyperplasia starting at Day 2, and it persisted for about 7 days. The urothelium regained normal histology 13 days after TPA treatment. TPA bound specifically and with high affinity to murine bladder mucosa and muscularis particulate preparations. Scatchard analysis of mucosal binding revealed a Kd of 0.82 nM; at saturation, 2.43 pmol were bound per mg protein. Since TPA binds specifically to urinary bladder epithelium, and the induction of ODC activity is one of the properties of tumor promoters, one may conclude that TPA may promote urinary bladder carcinogenesis. Intravesical saccharin also induced urinary bladder ODC activity, but TPA at equimolar quantity was far more potent than saccharin. Thus TPA, being a structurally well-defined molecule, may be a useful compound to study the phenomenon of the tumor promotion stage in urinary bladder carcinogenesis.
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PMID:Specific binding, stimulation of rodent urinary bladder epithelial ornithine decarboxylase, and induction of transitional cell hyperplasia by the skin tumor promoter 12-O-tetradecanoylphorbol-13-acetate. 631 23

Groups of C57Bl/6 (B6) mice (responsive) and DBA/2 (D2) (non-responsive) mice received an i.p. dose of benzo[a]pyrene (BP) (100 mg/kg body weight) with or without pretreatment with beta-naphthoflavone (BNF), an inducer of monooxygenases. The amount of mutagenic BP metabolites in the urine was determined by the Salmonella/microsome assay (strain TA100) and excretion of BP metabolites was quantified by h.p.l.c. After inducer treatment, the responsive mice excreted more mutagens and total oxidized BP metabolites in the urine than did the non-responsive strain. The ratio of BP diols:total oxidized metabolites was 0.42 in B6 mice and 0.72 in D2 mice and was not affected by inducer treatment. After a dose of [14C]BP, radioactivity was measured in the faeces for up to 7 days. The half-life of [14C]BP in the non-responsive D2 mice was about twice that in the responsive B6 mice. Our results agreed with a previously proposed model of the risk factors for toxic effects and/or the development of tumours after exposure to polycyclic aromatic hydrocarbons in responsive and non-responsive mouse strains.
Carcinogenesis 1984 Jan
PMID:Metabolism and urinary excretion of mutagenic metabolites of benzo[a]pyrene in C57 and DBA mice strains. 631 24

Several approaches were employed to investigate whether murine stock and strain differences in susceptibility to two-stage skin carcinogenesis are due to differences in the metabolism of the initiating aromatic hydrocarbons, or the consequences of the agents used for promotion. A cell-mediated mutagenesis assay was used to quantitatively compare the abilities of cultured newborn SENCAR, DBA/2, C57BL/6 and BALB/c keratinocytes to metabolize dimethylbenz[a]anthracene (DMBA) to mutagenic and cytotoxic metabolites. At equivalent concentrations of DMBA, throughout a 25-fold range in promutagen concentration, C57BL/6, BALB/c and SENCAR keratinocyte-dependent mutant frequencies were very similar and approximately twice DBA/2 keratinocyte-dependent mutant frequencies. In in vivo tumor studies, C57BL/6 mice were more sensitive than SENCAR mice to complete skin carcinogenesis protocols employing repetitive weekly treatments with DMBA and benzo[a]pyrene (BP). At equivalent concentrations of either DMBA or BP, C57BL/6 mice developed carcinomas sooner, and had a greater number of carcinomas per animal. SENCAR mice were very sensitive to two-stage skin carcinogenesis protocols employing BP and DMBA as initiators and benzoyl peroxide and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoters. C57BL/6 mice were relatively refractory to TPA promotion but sensitive to promotion with benzoyl peroxide. These findings suggest that murine stock and strain-dependent differences in sensitivity to two-stage skin carcinogenesis may not be due to major differences in the metabolism of the initiating hydrocarbons, but are partially the consequences of the agents used for promotion.
Carcinogenesis 1984 Mar
PMID:Murine susceptibility to two-stage skin carcinogenesis is influenced by the agent used for promotion. 632 45

Complex carbohydrates in premalignant lesions of mouse submandibular gland tumors were examined by the lectin-peroxidase conjugate method. Peroxidase-conjugated lectins of PNA, RCA-1, DBA, SBA, UEA-1 and WGA were used to detect specific sugar residues of complex carbohydrates in premalignant lesions during experimental carcinogenesis. Marked reduction of PNA and SBA bindings occurred in duct-like structures and cystic lesions which were transformed from granular convoluted tubule cells. Premalignant lesions bound slightly to PNA, RCA-1, DBA, SBA and WGA and manifested increased UEA-1 binding. Squamous metaplastic epithelia of premalignant lesions manifested increased binding to PNA, RCA-1 and SBA as compared to those of duct-like structure and cystic epithelia.
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PMID:Lectin-binding in premalignant lesions during submandibular gland carcinogenesis. 643 17

Mice of the inbred strain DBA/2 responded to a two-stage, initiation-promotion tumorigenesis protocol when high initiating doses (400 nmol/mouse) of 7,12-dimethylbenz[a]anthracene were utilized. They also responded when N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was used as the initiating agent. The tumor response in both cases was characterized by a rapid rate of tumor development with the maximal tumor responses reached on or before the 15th week of promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). When DBA/2 mice were compared with SENCAR mice for promotion sensitivity following initiation with MNNG, the two mouse stocks responded with a nearly identical tumor response. C57BL/6 mice were essentially resistant to TPA promotion regardless of the initiator or the dose of initiator used. A preliminary study was conducted to determine how susceptibility to tumor promotion by TPA was inherited in F1 mice derived from DBA/2 (sensitive) and C57BL/6 (resistant) parents. The B6D2F1 mice were as sensitive as the DBA/2 parent, suggesting that susceptibility in these two inbred mouse strains is inherited as an autosomal dominant trait. The results show that these two inbred mouse strains may provide a model system for studying genetic factors controlling susceptibility to phorbol ester skin tumor promotion.
Carcinogenesis 1984 Nov
PMID:DBA/2 mice are as sensitive as SENCAR mice to skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate. 643 2

The antitumor effect of lentinan in syngeneic and autochthonous tumor-host systems and its suppressive effect on 3-methylcholanthrene (MC)-induced carcinogenesis were confirmed using DBA/2 and SWM/Ms hosts. The regressive activity of lentinan against the solid form of Sarcoma 180 was the most effective in DBA/2, SWM/Ms, or A/J mice and less effective in C3H/He or C57BL/6 mice. The growth of a syngeneic MC-induced DBA/2.MC.CS-1 fibrosarcoma (native and trypsinized) was markedly inhibited, and the regression of tumors was detected by the i.p. injection of minute amounts of lentinan into DBA/2 mice, which were the most suitable host in lentinan treatment. When DBA/2 mice were used, lentinan was also effective for even autochthonous primary tumors induced within 15 weeks after MC inoculation, but less effective for tumors induced during the 16 to 36 weeks after MC treatment. Lentinan showed a prominent suppressive effect in MC-induced carcinogenesis using DBA/2 and SWM/Ms mice but not effect when BALB/c, C57BL/6, or C3H/He mice were used. The timing of lentinan administration in the latter result was examined using SWM/Ms mice, and lentinan, when it was given daily for 10 days after the third week of MC inoculation, was strikingly effective (33%), but not so effective (63%) when lentinan was given after the sixth week of MC treatment, compared with tumor-occurrence rate in the control group (88%). The reason why DBA/2, SWM/Ms, or A/J mice were suitable hosts for lentinan treatment is not clear, but the natural killer capability or phagocytic macrophage function in these strains seems to have no relation to lentinan action, because A/J mice are deficient in natural killer function, and in these strains of mice the phagocytic function of macrophages is weak. It may be quite possible that these strains of mice are most sensitive to delayed-type hypersensitivity and/or cytotoxic T-cell response in which T-cells and lentinan play important roles. The tumor-host systems presented here provide a good model in which lentinan retains an inhibitory capacity in syngeneic and autochthonous hosts, and such a model offers the possibility for further study of the host defense mechanism against cancer.
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PMID:Antitumor activity of lentinan in murine syngeneic and autochthonous hosts and its suppressive effect on 3-methylcholanthrene-induced carcinogenesis. 648 73

The capacity of the chemical carcinogen 2-acetylaminofluorene (AAF) and its derivates to cause DNA damage in primary mouse hepatocytes from aryl-hydrocarbon responsive C57BL/6 and non-responsive DBA/2 mice was studied using the alkaline elution technique. Low levels of DNA damage were observed after exposure of hepatocytes to either AAF or 2-aminofluorene (AF) (50-100 microM). Quantitation of metabolites produced from AAF in hepatocytes from untreated C57BL/6 and DBA/2 mice using h.p.l.c. showed a similar metabolic profile with respect to C- and N-hydroxylations. After in vivo pretreatment with the potent monooxygenase inducer TCDD (50 micrograms/kg), N-hydroxylation in the C57BL/6- and DBA/2-derived hepatocytes increased 25- and 5-fold, respectively. However, the C-hydroxylation pathways were still responsible for approximately 90% of the metabolism in cells from both strains. This may explain why only a slight increase in the DNA damage was observed in C57BL/6 mouse hepatocytes after incubation with AF or AAF and no increase in DNA damage was seen in the DBA/2 hepatocytes isolated from TCDD treated animals. Both N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-acetoxy-2-acetylaminofluorene (N- OAc -AAF) caused clear dose-dependent increases in DNA strand breaks (5-100 microM), suggesting that N-hydroxylation was the rate limiting step in the activation process of AAF leading to the DNA damage. Treatment of hepatocytes with paraoxon, an inhibitor of microsomal deacetylase activity, prior to exposure to either N-OH-AAF or N- OAc -AAF completely inhibited the damage caused by N-OH-AAF, while the damage caused by N- OAc -AAF was only partially inhibited. This suggests that these compounds are causing genotoxic effects after deacetylation. In accordance with this, N-hydroxy-2-aminofluorene (N-OH-AF), the deacetylated metabolite of N-OH-AAF, was an effective genotoxic agent, causing DNA strand breaks at low doses. Depletion of cellular glutathione by pretreatment with diethyl maleate, increased the sensitivity of the cells to the damage induced by N-OH-AF. These data indicate that glutathione may play an important role in the detoxification of N-OH-AF in mouse hepatocytes.
Carcinogenesis 1984 Jun
PMID:The genotoxicity of aromatic amines in primary hepatocytes isolated from C57BL/6 and DBA/2 mice. 672 87

The effect of supplemental selenium on 7,12-dimethylbenz[a] anthracene (DMBA)-induced mammary tumorigenesis was investigated in several mouse strains. Selenium, administered as SeO2 in the drinking water, inhibited mammary tumor formation in DMBA-treated (C57BL x DBA/2f)F1, C3H/StWi and BALB/c female mice. In addition, selenium inhibited the occurrence of DMBA-induced ductal hyperplasias in (C57BL x DBA/2f)F1 and BALB/c mice and mammary tumour virus-induced alveolar hyperplasias in BALB/cfC3H mice. Selenium did not alter the growth of established mammary tumors. These results demonstrate that supplemental selenium inhibits both chemical-and viral-induced mouse mammary tumorigenesis, and secondly, that the development of preneoplastic lesions, an early stage in mammary tumorigenesis, is very sensitive to selenium-mediated inhibition.
Carcinogenesis 1981
PMID:Selenium-mediated inhibition of 7,12-dimethylbenz[a]anthracene-induced mouse mammary tumorigenesis. 679 57

The influence of the enzymatic inducer beta-naphthoflavone (BNF) and of the inhibitors alpha-naphthoflavone (ANF) and 2-diethylaminoethyl-2,2-diphenylvalerate HCl (SKF 525-A) on the frequency of sister chromatid exchanges (SCE) induced by cyclophosphamide (CPA) was studied in vivo in C57BL/6J male mice. Neither inducer nor inhibitors substantially modified the SCE level induced by 5 or 10 mg/kg CPA. The enzymatic induction by BNF was effective as treated animals showed a reduced paralysis time by zoxazolamine whereas ANF appeared to be ineffective. The enzymatic inhibition by SKF 525-A was confirmed by a longer sleeping time in pentobarbital-treated mice and also by a longer paralysis in zoxazolamine-treated mice. The lower susceptibility to CPA-induced SCEs of C57BL/6J mice relative to DBA/2 strain observed in a previous work seems not to be simply related to Ah locus mediated metabolism.
Carcinogenesis 1983
PMID:Effect of enzymatic induction and inhibition on cyclophosphamide-induced sister chromatid exchange in vivo. 682 90


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