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

To investigate the interaction between tumor promoters and their cellular targets, 6 new fluorescent derivatives of indole alkaloid tumor promoter teleocidin were synthesized from (-)-indolactam V, and examined for induction of Epstein-Barr virus, binding ability to the TPA receptor on mouse skin and activation of protein kinase C. (-)-7-(2-N-Dansylaminoethyl)indolactam V (dansyl-ILV) had strong activities and proved to be a potent tumor promoter in a 2-stage carcinogenesis experiment. (-)-2-Formyl-7-decanoyl-indolactam V (FD-ILV) showed a weak but significant activity. The other 4 derivatives had little activity. Treatment of HeLa cells with dansyl-ILV and FD-ILV resulted in intense fluorescence in the entire cytoplasm and on the nuclear membrane. Inactive or less active derivatives with hydrophobicity similar to that of dansyl-ILV showed significant cytoplasmic fluorescence, and those far less hydrophobic than dansyl-ILV or far more hydrophobic than FD-ILV showed little fluorescence. This suggested that hydrophobicity rather than biological activity determines the cellular uptake of these fluorescent probes.
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PMID:Biological activities and cellular uptake studies of fluorescent derivatives of indole alkaloid tumor promoter teleocidin. 253 1

It is reported here that Sendai virus envelopes (SVE) can be used to transfect multiple copies of DNA segments of different varieties and size. This capability further increases the usefulness of SVE. In addition, the ability to simultaneously transfect multiple copies of different genome segments promises to be a powerful tool in the field of molecular biology. The simultaneous transfection of NEO gene and cytomegalovirus immediate early antigen gene was successfully done. Sendai virus envelopes (SVE)1 have been used successfully to study carcinogenesis of Epstein-Barr virus (1, 2). SVE have been shown to have a large carrying capacity (3) for the microinjection of macromolecules into target cells. SVE are hollow vesicles constructed from the viral proteins hemagglutinin HN and fusion factor F.
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PMID:Cotransfection of nucleic acid segments by Sendai virus envelopes. 253 42

A study of the repair of DNA damage in the dihydrofolate reductase (dhfr) gene of SV40-transformed human fibroblasts after treatment with 8-methoxypsoralen (8MOP) and UVA is described. 8MOP+UVA-induced cross-links in the dhfr gene were completely repaired by 12 h in one normal and one Fanconi's anaemia (FA) group A cell line. In contrast, approximately 35% of cross-links in an episomally maintained Epstein--Barr virus derived plasmid remained unrepaired even after 48 h. Cross-linkable monoadducts in the dhfr gene were repaired more slowly than cross-links, and there was no detectable repair of cross-linkable monoadducts in the plasmid. Thus the ability of a cell to repair 8MOP+UVA-induced cross-links or cross-linkable monoadducts in an episome does not reflect its capacity to repair such lesions in genomic DNA.
Carcinogenesis 1989 Jul
PMID:Repair of 8-methoxypsoralen + UVA-induced damage in specific sequences in chromosomal and episomal DNA in human cells. 254 11

In relation to the observed association of carcinogenesis with parasitic infections, the mutagenicity of extracts of Schistosoma japonicum and Clonorchis sinensis was examined. In the bacterial mutagenicity tests using the Ames Salmonella typhimurium strains TA98, TA100, TA97 and TA102, and Escherichia coli WP2 and WP2 uvrA pKM101 Schistosoma soluble egg antigen and a homogenate of adult Schistosoma worms showed no positive responses either in the presence or in the absence of S9 mix. Likewise, adult worm extracts of Clonorchis showed no mutagenicity. The Schistosoma soluble egg antigen showed a weak but significant activity for the induction of Epstein-Barr virus expression in viral genome-carrying human lymphoblastoid cells in culture. This phenomenon suggests that the soluble egg antigen possesses tumor-promoting activity.
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PMID:Evaluation of the mutagenicity and the tumor-promoting activity of parasite extracts: Schistosoma japonicum and Clonorchis sinensis. 255 10

The analysis of cancers associated with immunodeficiencies (either congenital, iatrogenic or acquired) enabled us to define the possible role of these deficiencies in the sequence of events leading to cancer and in particular the emergence of hematopoietic proliferations. Immunodeficiency increases the risk of viral infection, and in severe deficiencies, uncontrolled infections (Epstein-Barr virus) are directly responsible for the appearance of polyclonal proliferations; in moderately severe deficiencies, the hyperstimulation of the immune system by repeated infections increases the number of mutagenic events, but the immortalization of a malignant clone is a late event, which may or may not be linked to a viral infection. On the other hand, some intrinsic congenital or acquired abnormalities of lymphoid cells may be responsible both for immunodeficiency and carcinogenesis (chromosomic fragility). Apart from any immunological reaction, the immune system plays a role in the proliferation and differentiation events in various tissues; and any dysregulation of the latter may indicate the emergence of a cancer.
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PMID:[Immunodeficiency and cancer]. 267 65

We investigated the relationship between the ability to repair the O6-alkylguanine lesions and sister chromatid exchange (SCE) induction. Six human lymphoblastoid cell lines, with O6-alkylguanine alkyltransferase (AGT) activities ranging from 0 to 13.2 fmol/micrograms DNA, were tested for their sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-, methyl methanesulfonate (MMS)- and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-induced SCEs. L33, a long established lymphoblastoid cell line with no AGT activity, was sensitive to all three alkylating agents. In the other more recently established Epstein-Barr virus transformed cell lines, no correlation between AGT activity (ranging from 2.4 to 13.2 fmol/micrograms DNA) and sensitivity to MMS or MNNG was noted. In fact, of these five cell lines, the cell line with the highest AGT activity, line 852A, was the most sensitive to MNNG-induced SCEs. While cell lines differed in overall alkylation by MNNG, no relationship between overall akylation and sensitivity to MNNG-induced SCE formation was noted. In contrast to the results with the monofunctional alkylating agents, there was a correlation between AGT activity and BCNU-sensitivity to SCE induction. Cell lines with low AGT activities were more sensitive to the bifunctional alkylating agent than cells with higher activities. Therefore, while DNA interstrand cross-links produced by BCNU exposure probably underlie SCE induction by this agent, the lesions and processes that lead to SCE induction after exposure to monofunctional alkylating agents remain unclear.
Carcinogenesis 1989 Apr
PMID:The relationship between O6-alkylguanine alkyltransferase activity and sensitivity to alkylation-induced sister chromatid exchanges in human lymphoblastoid cell lines. 270 16

Mechanical wounding provides a convertogenic ("stage I tumor-promoting") stimulus in initiated NMRI mouse skin, indicating that this stage of carcinogenesis can be entirely controlled by endogenous factors. A search for such factors led to the finding that both platelet-derived Epstein-Barr-virus-inducing factor (EIF), alias human TGF beta 1 and porcine TGF beta, exhibited--upon intracutaneous injection--convertogenic efficacy in initiated NMRI-mouse skin in vivo provided that their injection was combined with a single topical application of the non-convertogenic tumor promoter 12-O-retinolyphorbol-13-acetate (RPA). Since TGF beta inhibits epidermal cell proliferation, the RPA treatment is thought to provide a mitogenic stimulus required for conversion. The RPA treatment can be replaced by intracutaneous injection of transforming growth factor alpha (TGF alpha). These results indicate that the stage of conversion consists of two components, one of which is related to mitogenesis (RPA or TGF alpha), the other to a still unknown activity exhibited by TGF beta-like factors. Thus, endogenous factors with the quality of "wound hormones" may be involved in multistage skin carcinogenesis. This finding could explain the convertogenic effect of skin wounding.
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PMID:Stimulatory role of transforming growth factors in multistage skin carcinogenesis: possible explanation for the tumor-inducing effect of wounding in initiated NMRI mouse skin. 271 98

Previous studies have demonstrated that approximately one-third of human lymphoblastoid cell lines (LCLs) are deficient in removing O6-methylguanine residues because of the lack of O6-alkylguanine-DNA alkyltransferase (O6-AGT) activity. Such LCLs have been designated Mex-, while the proficient LCLs are Mex+. Our determinations of O6-AGT activity as a function of cellular protein concentration on 37 previously-established LCLs disclosed that the expression of the enzyme was high in 14 (Mex+) and barely detectable in 16 (Mex-). The other seven LCLs showed intermediate activity of the enzyme. By contrast, all of the 28 LCLs that we newly established contained high enzyme activity, implying that they consisted of mainly Mex+ cells. Since the conventional O6-AGT assay on Mex+ cell populations was not capable of detecting the co-existence of Mex- cells as a minor component, we attempted to determine the proportion of Mex- phenotype in newly-immortalized lymphoblastoid cell clones which had been established directly on semisolid agar. All of the 15 independent clones derived from a single blood sample also showed high O6-AGT activity, rendering it unlikely that Epstein-Barr virus transformation per se was responsible for the generation of Mex- LCLs. These results collectively indicate that Mex+ cells predominate in LCLs shortly after establishment and also suggest that the possible growth advantage for Mex- cells should play an important role in the subsequent development of Mex- LCLs during the long-term culture in vitro.
Carcinogenesis 1989 Nov
PMID:Predominance of Mex+ cells in newly-established human lymphoblastoid cell lines. 280 28

Epstein-Barr virus (EBV) activation of latent infection and traditional life styles, especially food habits, have been strongly associated with an increased risk of nasopharyngeal carcinoma (NPC) in humans. On the basis of anthropological studies in Tunisia, southern China and Greenland, extracts of representative preserved food items consumed frequently by the high-risk populations for NPC were assayed for the presence of EBV activators in Raji cells. A strong EBV activation activity was observed in aqueous extracts of some Cantonese salted dried fish from China, harissa (a spice mixture) and to a lesser extent qaddid (dry mutton preserved in olive oil) from Tunisia. These new data may support epidemiological evidence for the importance of Cantonese salted and dried fish and other food items in the etiology of NPC.
Carcinogenesis 1988 Aug
PMID:Epstein-Barr virus activation in Raji cells by extracts of preserved food from high risk areas for nasopharyngeal carcinoma. 284 Oct 48

The recognition of Burkitt lymphoma (BL) as a clinical syndrome and a pathological entity in African children resulted from astute clinical observations (bedside epidemiology), the availability of cancer registry data and accurate pathological interpretation. Following the early studies in Africa, it soon became evident that this tumor occurred worldwide and the excess of cases in Africa was an incidence phenomenon associated with specific environmental factors. The sentinel discovery of the Epstein Barr virus (EBV) and its association with BL stimulated a wide variety of scientific investigations which have had an impact of virtually every discipline and biology. Epidemiological observations linked to modern laboratory techniques have provided etiological insights which implicate specific environmental factors and genetic events in the pathogenesis of BL and other immunoproliferative diseases. Early infection with EBV and holoendemic malaria are clearly of paramount importance in the development of endemic BL (eBL). These factors do not play a role in the majority of sporadic BL (sBL) cases, but immunosuppression and T-cell deregulation almost certainly are common denominators. The final or principle genetic event in both instances would appear to be the chromosome 8 translocation involving the c-myc oncogene and structural alteration. It is expected that the BL model will continue to be a useful one for identifying basic mechanisms in carcinogenesis which may be applicable as well to a variety of non-neoplastic diseases.
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PMID:Malignant lymphoma in African children: three decades of discovery. 285 87


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