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

Mutation and malignant transformation were followed in the same cells. Mouse fibroblasts (C3H 10T 1/2) were mutated and transformed by 4-nitroquinoline-1-oxide with similar, approximately linear dose-responses. The presence of caffeine immediately after exposure to 4-nitroquinoline-1-oxide potently inhibited mutation and transformation at high but not at low doses of 4-nitroquinoline-1-oxide. Whilst the coordinate induction of mutation and transformation could be explained by both a common target (DNA) or a common reactive species hitting several targets, the identical modulation by a DNA repair inhibitor of both end points suggests fundamental similarities in the nature of the lesions leading to mutation and transformation and in the processing of these lesions, implying DNA as target and mutation as one (but not necessarily the sole) required step in transformation.
Carcinogenesis 1981
PMID:Coordinate mutation and transformation of mouse fibroblasts: induction by nitroquinoline oxide and modulation by caffeine. 679 16

Caffeine inhibits the activity of DNA polymerase I (E. coli) and its proteolytic large fragment in in vitro DNA replication system. DNA polymerase from Micrococcus luteus is also equally inhibited by caffeine. The extent of inhibition was more with the activated adenovirus, T4 and calf thymus DNA than with synthetic DNA template-primers. Results obtained from time-course studies indicated that caffeine inhibition reached maximum by 30 min of incubation. Enzyme kinetic studies showed that inhibition was competitive with respect to DNA template.
Carcinogenesis 1982
PMID:Caffeine inhibits DNA polymerase I from Escherichia coli: studies in vitro. 703 55

A single large dose of caffeine (100 microgram/g body weight) was injected at different time in relation to urethan initiation for skin tumorigenesis, topical anthranil treatment serving as promotor. Caffeine significantly increased papilloma incidence when given 6 h before initiation, and to an insignificant extent, at 9 h prior to initiation. A tendency for inhibition was evident when caffeine was administered 6 h after urethan but this was also not statistically significant. Lung adenoma induction by urethan was unaffected. The significance of the timing of caffeine treatment in modifying the outcome of the initiation phase is discussed.
Carcinogenesis 1981
PMID:The effect of caffeine on two-stage skin carcinogenesis and on complete systemic carcinogenesis. 729 65

The effect of caffeine on cell killing, mutation induction, DNA repair, and inhibition of DNA synthesis was investigated in a clonal derivative of M3-1 Chinese hamster cells after treatment with N-ethyl-N-nitrosourea (ENU). Caffeine enhanced cell killing but had no effect on the mutation frequency/viable cells for the two genetic markers, 6-thioguanine resistance and ouabain resistance. The removal of ethylated purine bases from DNA was as follows: most of the 3-ethyladenine was lost in 20 h (greater than 85%) and approximately 45% of the 7-ethylguanine was lost in 45 h, whereas 75--93% of the O6-ethylguanine was still present at this time. Caffeine did not seem to influence these rates significantly. The ENU-induced inhibition of DNA synthesis was reversed by caffeine. It is concluded that the potentiation of ENU-induced cell killing by caffeine is caused by the increased frequency of DNA replication past damaged sites in parental DNA.
Carcinogenesis 1981
PMID:Effect of caffeine on cell killing, mutation induction, DNA repair, and DNA synthesis after treatment with ethylnitrosourea. 732 26

The effects of sodium saccharin and caffeine on urinary bladder carcinogenesis in Wistar strain rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were studied. Animals were given 0.01% BBN as an initiator for 4 weeks and then sodium saccharin and/or caffeine as promoters for 32 weeks (Experiment I), or were treated simultaneously with 0.001% BBN, sodium saccharin and/or caffeine for 40 weeks (Experiment II). The urinary bladders were then removed and examined by light and electron microscopy. Sequential administration of sodium saccharin after BBN significantly enhanced the induction of hyperplasias compared with administration of BBN alone (Experiment I), and simultaneous administration of sodium saccharin with BBN significantly enhanced the induction of hyperplasia and papillomas compared with BBN alone (Experiment II). Two types of hyperplasias developed in the urinary bladder of rats treated with sodium saccharin alone in both experiments. Caffeine alone had no effect on the rat urinary bladder epithelium, and either sequential or simultaneous administration of caffeine with BBN caused no marked enhancement of carcinogenesis in these experiments.
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PMID:Effects of sodium saccharin and caffeine on the urinary bladder of rats treated with n-butyl-n-(4-hydroxybutyl)nitrosamine. 742 86

Heterocyclic aromatics amines (HAAs), such as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), are metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2). We examined the relationship between CYP1A2 and NAT2 activity and the excretion of total unconjugated MeIQx in 66 healthy subjects. The subjects ate a control diet for 7 days containing lean ground beef cooked at low temperature. On day 8, they were tested for CYP1A2 and NAT2 activity by caffeine phenotyping. On the evening of day 8, subjects consumed lean ground beef cooked at high temperature containing 9.0 ng of MeIQx/g of meat. The subjects ate 3.1-4.0 g meat/kg body wt. Twelve-hour urine samples were collected and MeIQx was measured by gas chromatography-mass spectrometry. Using linear regression analyses, we found that higher CYP1A2 activity was associated with lower levels of total unconjugated MeIQx in the urine (P = 0.008) when adjusted for amount of meat eaten, while NAT2 activity showed no relationship with the latter. This suggest that a greater percentage of MeIQx is converted to metabolites such as the N-hydroxy derivative when CYP1A2 activity is higher. This finding supports the concept that inter-individual variation is CYP1A2 activity may be relevant for cancers associated with exposure to HAAs.
Carcinogenesis 1995 Nov
PMID:Lower levels of urinary 2-amino-3,8-dimethylimidazo[4,5-f]-quinoxaline (MeIQx) in humans with higher CYP1A2 activity. 758 10

We have studied the effect of caffeine on gene- and strand-specific DNA repair after exposure of Chinese hamster ovary cells and human xeroderma pigmentosum complementation group C (XPC) cells to ultraviolet irradiation (UV). In hamster cells, caffeine inhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by up to 66% after 8 h of repair incubation. This effect was dose-dependent, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster DHFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysis. In hamster cells, caffeine caused a modest enhancement of repair. Caffeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in early S phase during the 24 h post-irradiation period. In XPC cells, 10 mM caffeine inhibited the removal of CPDs from the transcribed strand of the DHFR gene by 92%. The removal of all photoproducts from the overall genome was inhibited by 26% in these cells. Since the residual repair in XPC cells is thought to occur in active genomic regions, we propose that caffeine preferentially inhibits gene-specific repair.
Carcinogenesis 1995 May
PMID:Caffeine inhibits gene-specific repair of UV-induced DNA damage in hamster cells and in human xeroderma pigmentosum group C cells. 776 78

A series of 16 experiments, using a total of 2,000 BD6 rats, was designed in order to assess the ability of 8 individual agents or their combinations to modulate the liver and oesophageal carcinogenesis induced by multiple doses of diethylnitrosamine (DEN). Of the antioxidants tested, sodium selenite, ascorbic acid, and butylated hydroxytoluene generally exhibited protective effects on both types of tumors. In contrast, retinoic acid behaved as a promoter of DEN hepatocarcinogenesis, but this effect could be eliminated by its combination with either selenite or butylated hydroxytoluene. Caffeine and theophylline, when individually assayed, were devoid of significant protective effects, and the latter methylxanthine stimulated oesophageal tumorigenesis when administered after exposure to the carcinogen. Caffeine tended to decrease the multiplicity of liver tumors and potentiated the inhibitory effect of selenite in the liver. Irrespective of combination with caffeine, treatment with phenobarbital before each DEN injection tended to reduce the multiplicity of both liver and oesophageal tumors. On the other hand, the metabolic inhibitor diethyldithiocarbamate, given after each DEN injection, dramatically enhanced the incidence and multiplicity of oesophageal tumors. Thus, on the whole, modulation of DEN carcinogenesis varied depending on test agents, their combinations, dosages, treatment schedules, and target organ.
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PMID:Modulation of diethylnitrosamine carcinogenesis in rat liver and oesophagus. 789 Aug 4

We have studied the ability of 8-methoxycaffeine (8-MOC)--one of the most effective caffeine derivatives in inducing chromosomal aberrations--to induce DNA double strand breaks (DSB) in purified human T lymphocytes during the cell cycle. Etoposide- or ellipticine-mediated DNA break frequency was used as a parameter of topoisomerase II activity. DNA-DSB induced by either 8-MOC or VP16 or ellipticine rose co-ordinately with the level of DNA topoisomerase II and with the onset of DNA replication. At concentrations between 10 and 50 microM 8-MOC was approximately 75% as active in terms of DSB as VP16 and ellipticine. By contrast with VP16 and ellipticine, 8-MOC was not cytotoxic. In conclusion, our data suggest that 8-MOC is an agent that efficiently induces DNA-DSB at non-toxic concentrations, and without direct inhibition of topoisomerase II.
Carcinogenesis 1994 Nov
PMID:Induction of DNA double-strand breaks by 8-methoxycaffeine: cell cycle dependence and comparison with topoisomerase II inhibitors. 795 97

To determine which of the N-acetyltransferase (NAT) alleles [monomorphic (NAT1) or polymorphic (NAT2)] are expressed in the target cells for arylamine carcinogenesis, namely normal human uroepithelial cells, cDNA was prepared from cellular RNA and amplified by polymerase chain reaction (PCR), using upstream primer 1 comprising the 5' end (nt 47-68) and either downstream primers 2 (nt 908-889) or 3 (nt 953-931) corresponding with the 3' end. With primers 1 and 2, selective for NAT1, a characteristic 861 bp DNA fragment was obtained, whereas with primers 1 and 3, selective for NAT2, a characteristic 907 bp fragment was formed. Similarly, the PCR-amplified cDNA products from the SV40-immortalized human uroepithelial cell line were also found to contain both NAT1 and NAT2. Restriction fragment length polymorphism (RFLP) analysis with HincII (digesting NAT2 to produce 659 bp and 248 bp fragments) and HindIII (digesting NAT1 to produce a 786 bp fragment) further confirmed the authenticity of the NAT alleles. Furthermore, the NAT genotypes of 38 individuals were determined by PCR amplification of lymphocyte DNA and subsequent RFLP analysis using TaqI, KpnI and BamHI. The genotypes were compared to their in vivo acetylator phenotypes which were determined by measuring 5-acetylamino-6-formylamino-3-methyluracil and 1-methylxanthine in urine following administration of caffeine. A good correlation between the genotype and phenotype was obtained in the study population and the frequency of NAT2 allele distribution was M1 > wild-type > M2 > M3. These results suggest that susceptibility to arylamine-induced bladder cancer might be influenced by both hepatic and bladder NAT and that the NAT genotype might be a useful biomarker for screening high risk individuals for bladder cancer resulting from exposure to arylamines.
Carcinogenesis 1994 Dec
PMID:Expression of N-acetyltransferase (NAT) in cultured human uroepithelial cells. 800 Dec 35


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