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

In order to gain an insight into the nature of the radiomimetic activity by which the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) alters cell cycle parameters in HeLa cells, possibilities of modifying the TPA-induced G2 block and recovery from it were studied. TPA-induced G2 blockage was analysed by counting mitotic figures. It was not influenced by hydroxyurea (10(-3) M) thus indicating that it is independent of DNA synthesis. TPA-induced decrease of mitotic activity occurred faster than that caused by cycloheximide (10(-5) M) indicating that the TPA-sensitive transition point in G2 is closer to mitosis than that for cycloheximide. Superoxide dismutase, catalase, alpha-tocopherol, the radioprotector S-(2-aminoethyl)isothiuroniumbromide.HBr (AET), caffeine and indomethacin and eicosatetraynoic acid (ETYA), both inhibitors of oxygenases in the arachidonic acid cascade, were not capable of reducing the TPA-induced G2 response. Under certain conditions small concentrations of AET (10(-8) M) and ETYA (10(-8) M) appeared to improve recovery slightly. Mannitol and sorbitol, however, both hydroxyl radical scavengers at 0.1 M concentration reduced TPA-effectiveness to a large degree (0.1 M D- and L-mannose were ineffective). Dimethylsulfoxide (0.1 M), another hydroxyl radical scavenger, was ineffective.
Carcinogenesis 1985 Sep
PMID:Mechanistic aspects of the delay in the G2 phase of the cell cycle caused by tumor promoter 12-O-tetradecanoylphorbol-13-acetate in HeLa cells. 402 35

With the view of studying the role of autonomic nervous system in chemical carcinogenesis mechanism in outbred white male rats, chronically treated with NDEA, there has been investigated the modifying effect of some neurotropic pharmacological drugs which cause either stimulation or inhibition of: 1. adrenergic processes (noradrenalin, isoproterenol, clonidine, pyrroxane and propranolol); 2. cholinergic processes (proserine and atropine); 3. the function of the central nervous system (CNS)--caffeine and ethanol. Pharmacological activation of alpha-adrenoreceptors or blocking of both beta-adrenoreceptors and cholinoreceptors has been revealed to stimulate hepatocarcinogenesis. On the contrary, the administration of alpha-adrenoreceptors antagonist or beta-adrenoreceptor and cholinoreceptors agonists inhibited the process of carcinogenic transformation. Caffeine, being the CNS stimulator, has significantly promoted carcinogenesis, while ethanol has practically prevented NDEA effect. Clonidine has also demonstrated its anticarcinogenic action. The obtained data are being discussed in connection with chemical carcinogenesis influence upon the CNS integrative function in control and regulation of tissue homeostasis.
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PMID:On participation of the autonomic nervous system in the mechanisms of chemical carcinogenesis. 612 35

The cytotoxic effect of 4-nitroquinoline-1-oxide (4NQO) on cultured Chinese hamster cells was drastically reduced by the presence of caffeine (0.2-1 mM). Caffeine, however, did not reduce the cytotoxicity of 4-hydroxyaminoquinoline-1-oxide (4HAQO), an active metabolite of 4NQO. The 105 000 g supernatant from the cell homogenate could catalyze the conversion of 4NQO to 4HAQO in the presence of NADPH or NADH as a hydrogen donor. This enzyme activity was strongly inhibited by caffeine (0.1-10 mM) or dicumarol (10(-8)-10(-6) M), an inhibitor of DT diaphorase (E.C.1.6.99.2). Dicumarol also reduced the cytotoxicity of 4NQO. These results clearly suggest that caffeine inhibits the conversion step of 4NQO to 4HAQO, resulting in a decrease in the cytotoxicity of 4NQO. Furthermore, the frequency of 6-thioguanine-resistant mutation by 4NQO was also strongly reduced by the presence of caffeine (1 mM) in cultured Chinese hamster cells, being consistent with the results of cytotoxicity.
Carcinogenesis 1984 Mar
PMID:Caffeine inhibition of the metabolic activation of a carcinogen, 4-nitroquinoline-1-oxide, in cultured Chinese hamster cells. 620 Feb 48

The effect of exposing mice to both a chemical carcinogen and leukemia virus with and without an inhibitor of DNA repair were compared. The data indicated that benzo[a]pyrene (BP) could exert a potentiating effect of Friend viral leukemogenesis in mice, which was dependent on the relative times of administration of the chemical and virus. The addition of caffeine as an inhibitor of DNA repair further enhanced the potentiating effect of BP on the leukemia, but in the absence of BP, caffeine showed no carcinogenic effect either when given alone or in conjunction with Friend leukemia virus.
Carcinogenesis 1981
PMID:Potentiating effect of benzo[a]pyrene and caffeine on Friend viral leukemogenesis. 626 20

The effects of caffeine on pancreatic tumorigenesis by 4-hydroxyaminoquinoline 1-oxide (4-HAQO) and on pancreatic DNA synthesis were studied in partially pancreatectomized male Wistar rats. 4-HAQO was injected i.v. as a single dose of 7 mg/kg body weight 3 days after partial pancreatectomy. Caffeine was injected s.c. every 12 h at the maximum tolerated dose (m.t.d.) of 120 mg/kg body weight, half the m.t.d., and one quarter the m.t.d. from 12 to 72 h before and 0 to 72, 72 to 132, and 0 to 132 h after 4-HAQO treatment. Post-treatment with caffeine from 0 to 132 h had a dose-dependent biphasic effect on pancreatic tumorigenesis: post-treatment with the m.t.d. of caffeine decreased the total number of nodules, whereas treatment with one quarter the m.t.d. of caffeine increased their number. Decrease in the number of nodules was also observed on post-treatment with the m.t.d. of caffeine from 0 to 72 or from 72 to 132 h. Pretreatment with the m.t.d. of caffeine had no significant effect on the number of nodules. Recovery of pancreatic DNA synthesis was slower after simultaneous treatment with the m.t.d. of caffeine and 4-HAQO than after treatment with 4-HAQO alone. The possible mechanism of the effect of caffeine on pancreatic tumorigenesis induced by 4-HAQO in rats is discussed.
Carcinogenesis 1983
PMID:Effects of caffeine on pancreatic tumorigenesis by 4-hydroxyaminoquinoline 1-oxide in partially pancreatectomized rats. 640 1

To learn the effects of tumor inhibitors on chemically induced malformations, caffeine, antipain, and 13-trans-retinoic acid were given to pregnant ICR/Jcl mice after a single dose of urethan, N-hydroxyurethan, N-methyl-N-nitrosourea, N-ethyl-N-nitrosourea, or 4-nitroquinoline 1-oxide, which induces about 50% of the malformed fetuses. When caffeine was given immediately after carcinogen treatment on Day 10, urethan- and N-ethyl-N-nitrosourea-induced malformations were significantly suppressed by caffeine posttreatment, while N-hydroxyurethan- and N-methyl-N-nitrosourea-induced malformations were not suppressed by caffeine. 4-Nitroquinoline 1-oxide-initiated teratogenesis was also suppressed, but not significantly so (p not equal to 0.07). The results were very similar to those of the effects of caffeine on tumors induced by these carcinogens. Malformations of genetic origin (cleft palates and cleft lips) in CL/Fr mice were also suppressed significantly by caffeine treatment on Days 8 to 11, although the level of inhibition was less than that in chemically induced malformations. A protease inhibitor (antipromotor), antipain, also suppressed urethan-induced malformations. The antiteratogenic effects of antipain were most effective when it was given during the period of 24 to 48 hr after urethan treatment, while those of caffeine were most effective when it was given immediately after urethan. The promoting process might be involved in chemically induced teratogenesis, as it was in carcinogenesis. A natural retinoid (13-trans-retinoic acid) also suppressed urethan-induced malformations. Thus, tumors and malformations induced by chemical carcinogens were suppressed by tumor inhibitors, suggesting the similarity of both processes in the subcellular level, in spite of their morphological differences.
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PMID:Antiteratogenic effects of tumor inhibitors, caffeine, antipain, and retinoic acid in mice. 641 55

The promoting effects of various chemicals on urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Male Fischer 344 rats were given BBN at 0.01% or 0.05% in their drinking-water for four weeks. One of the following chemicals was then administered in the diet for 32 or 34 weeks: acetazolamide, allopurinol, phenobarbital, phenacetin, ortho-phenylphenol, sodium ortho-phenylphenate, diphenyl, sodium L-ascorbate, butylated hydroxyanisole, butylated hydroxytoluene, sodium saccharin, aspartame, sodium cyclamate, stevioside, DL-tryptophan, quercetin, caffeine, nicotine and hippuric acid. Phenacetin, sodium ortho-phenylphenate, sodium L-ascorbate and butylated hydroxyanisole were significant promoters of urinary bladder neoplasia in rats initiated with BBN. Sodium saccharin, diphenyl, butylated hydroxytoluene, allopurinol, and DL-tryptophan caused moderate or slight promotion of neoplastic changes in the experimental animals. No change in tumour yield was observed after administration of the other chemicals.
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PMID:Drugs, food additives and natural products as promoters in rat urinary bladder carcinogenesis. 653 4

Rats concomitantly fed N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT) and phenothiazine, or concomitantly fed FANFT and Glucaron then fed Glucaron alone had significantly greater incidences of transitional cell carcinomas of the bladder than rats fed FANFT alone. Caffeine and cysteamine did not affect FANFT bladder carcinogenesis. Phenothiazine induced nitroreductase activity of hepatic microsomes.
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PMID:Enhancement by phenothiazine and 2,5-di-O-acetyl-D-glucosaccharo-(1,4)(6,3)-dilactone of bladder carcinogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide in rats. 654 59

I.p. administration of caffeine led to a significant increase in hepatic ornithine decarboxylase activity in rats. The enzyme activity reached approximately 10-fold above the control level 5 h after the injection of caffeine at a dose of 150 mg/kg body weight. The high level of ornithine decarboxylase activity remained for 3 h and then decreased rapidly. The enzyme activity of the kidney, however, was not significantly enhanced by the administration of caffeine. The possible mechanism of the caffeine-mediated hepatic ornithine decarboxylase induction is discussed.
Carcinogenesis 1984 Feb
PMID:Induction of hepatic ornithine decarboxylase by intraperitoneal administration of caffeine in rats. 669 46

Aflatoxin B1 (AFB1) is activated by a rat microsomal extract (S-9) to form a product that inhibits DNA synthesis in HeLa cells. At 10(-7) M, AFB1 inhibited initiation of replicons, as shown in alkaline sucrose gradient profiles 30 min after incubation with the drug. Ninety minutes later, the profile of treated cells was similar to that of control, but 4 h later there was another effect on replicon initiation. At 10(-6) M, the inhibition of initiation was greater than at 10(-7) M and increased progressively. Four hours after removal of the drug, the gradient profile showed low amounts of radioactivity in all size classes of DNA. When cells were incubated in medium containing caffeine (2mM) even as late as 60 min after incubation with AFB1, the inhibition of replicon initiation was prevented. If caffeine was later removed from the medium, replicon initiation was then inhibited. At 10(-7) M or 10(-6) M, AFB1 had little immediate effect on chain elongation, but at 10(-5) M, the gradient profiles showed an accumulation of low molecular weight DNA molecules, with no radioactivity in the region of high molecular weight DNA, owing to a block to chain elongation; this was not affected by caffeine. These results suggest that AFB1 induces damage that changes the conformation of chromatin so that initiation of new replicons cannot occur; in the presence of caffeine this change does not occur and DNA replication is not inhibited.
Carcinogenesis 1981
PMID:Effects of activated aflatoxin B1 and caffeine on DNA replicon initiation in HeLa cells. 679 54


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