Carcinogenesis

https://academic.oup.com/carcin

List of Papers (Total 1,603)

Sensing and repairing DNA double-strand breaks

The DNA double-strand break (DSB) is the principle cytotoxic lesion for ionizing radiation and radio-mimetic chemicals but can also be caused by mechanical stress on chromosomes or when a replicative DNA polymerase encounters a DNA single-strand break or other type of DNA lesion. DSBs also occur as intermediates in various biological events, such as V(D)J recombination in...

Carcinogenic aristolochic acids upon activation by DT-diaphorase form adducts found in DNA of patients with Chinese herbs nephropathy

Aristolochic acid (AA), a naturally occurring nephrotoxin and rodent carcinogen, has recently been associated with the development of urothelial cancer in humans. Understanding which enzymes are involved in AA activation and/or detoxication is important in the assessment of an individual susceptibility to this natural carcinogen. We examined the ability of enzymes of rat renal...

Growth inhibition, cell-cycle arrest and apoptosis in human T-cell leukemia by the isothiocyanate sulforaphane

Glucosinolates (GL) can inhibit, retard or reverse experimental multistage carcinogenesis. When brassica plant tissue is broken, GLs are hydrolyzed by the endogenous enzyme myrosinase (Myr), releasing many products including isothiocyanates (ITC). Synthetic ITCs like sulforaphane exert chemopreventive effects against chemically induced tumors in animals, modulating enzymes...

Malignant conversion of non-tumorigenic murine skin keratinocytes overexpressing PACE4

Proprotein convertases (PCs) have been implicated in tumor cell invasion by processing a variety of substrates including matrix metalloproteinases (MMPs). PACE4, a member of the family of PCs was shown to enhance mouse skin carcinoma progression by increasing tumor cell invasiveness. However, the effects of PACE4 on malignant conversion have not been investigated. In the present...

p53–Mdm2—the affair that never ends

The p53–Mdm2 paradigm represents the best-studied relationship between a tumor suppressor gene which functions as a transcription factor and an oncogene, which functions primarily as an E3 protein ligase. The intimate relationship between these two partners has expanded to include almost every cellular biological system – from development, to growth control and programmed cell...

Mechanism of lovastatin-induced apoptosis in intestinal epithelial cells

We earlier showed that lovastatin potentiated the chemopreventive effects of sulindac against colon neoplasia in a rodent model and augments apoptosis induced by 5-FU and cisplatin in human colon cancer cells. In the present study, we investigated effects of lovastatin in spontaneously immortalized rat intestinal epithelial cells, IEC-18 and their K-ras transformed clones...

Effects of dairy products on heterocyclic aromatic amine-induced rat colon carcinogenesis

Heterocyclic aromatic amines (HAA) are initiating agents of colon carcinogenesis in animals and are suspected in the aetiology of human colon cancer. In the context of prevention, it seems interesting to test possible protective compounds, such as fermented milk, against HAA food carcinogens. Male F344 rats were used in a model of HAA-induced colon carcinogenesis. The HAA, 2...

Effects of genetic background on prostate and taste bud carcinogenesis due to SV40 T antigen expression under probasin gene promoter control

The incidence of prostate carcinomas in African–American men is greater than in white men, indicating genetic factors are involved in risk of this neoplasia. Recently, we have developed a transgenic rat model of prostate cancer, featuring development of malignancies within 15 weeks of age at very high incidence. Male transgenic rats with a Sprague–Dawley genetic background were...

Gene–environment interaction and aetiology of cancer: what does it mean and how can we measure it?

One form of defence against cancer development involves a series of genes whose role is to metabolize and excrete potentially toxic compounds and to repair subtle mistakes in DNA. Much laboratory and epidemiological research over the past decade has concentrated on the identification of these genes and an assessment of their role in cancer aetiology. Of particular interest has...

Skilled use of DNA polymorphisms as a tool for polygenic cancers

Association studies are assumed to be an efficient method of deciding whether a gene or its variant is important for cancer. Sequencing data on 30 000 human genes suggest that an average gene contains one to two single nucleotide polymorphisms (SNP), and high through-put technologies have become available for fast genotyping. Because no functional data are available for most SNPs...

Overexpression of αvβ6 integrin in serous epithelial ovarian cancer regulates extracellular matrix degradation via the plasminogen activation cascade

Recent evidence suggests that integrins are involved in the multi-step process of tumour metastasis. The biological relevance of αv integrins and associated β-subunits in ovarian cancer metastasis was examined by analysing the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). β1...

Immunohistochemical detection of malondialdehyde–DNA adducts in human oral mucosa cells

Malondialdehyde (MDA) is a major lipid peroxidation product that is mutagenic and tumorigenic. MDA-modified DNA adducts have been detected in animal and human tissues and may be a marker of human cancer risk. An immunohistochemical method, using a previously generated monoclonal antibody specific for MDA–DNA adducts, has been developed for the detection and quantification of DNA...

Photocarcinogenesis in human adult skin grafts

It has been demonstrated previously that the exposure to 7,12-dimethyl[ a ]benzanthracene (DMBA) and UVB radiation leads to the development of epidermal cysts, squamous cell carcinomas (SCC), melanocytic hyperplasia and melanoma in human foreskins from newborns grafted to immunodeficient mice. Improved techniques in grafting full-thickness skin from adults have enabled us to...

Acquisition of apoptotic resistance in arsenic-induced malignant transformation: role of the JNK signal transduction pathway

This study examined the role of signal transduction and apoptosis in malignant transformation induced by arsenic. Prior study showed that chronic arsenite exposure (500 nM, │18 weeks) induced malignant transformation in rat liver TRL 1215 cells. In the present work, these transformed cells were compared with passage-matched control cells. In addition, TRL 1215 cells were treated...

Induction of cyclooxygenase-2 by tumor promoters in transformed and cytochrome P450 2E1-expressing hepatocytes

The induction of cyclooxygenase (COX)-2 expression has been implicated as a mechanism for the formation of non-hepatic tumors. Recent investigations have demonstrated COX-2 expression in human hepatocellular carcinomas, but little is known about the regulation of hepatocyte COX-2 expression. Employing the adult, rat hepatocyte line RALA255-10G, the effects of cellular...

Induction of cell cycle arrest and apoptosis in human colon adenocarcinoma cell lines by β-carotene through down-regulation of cyclin A and Bcl-2 family proteins

Although the pharmacological role of β-carotene in the prevention and treatment of colon cancer has received increasing attention, little is known about the molecular mechanisms of action of this carotenoid. The present study demonstrates that β-carotene, a natural pigment widely present in fruit and vegetables, inhibits the growth of several human colon adenocarcinoma cell lines...

Mechanisms of tolerance to DNA damaging therapeutic drugs

The cytotoxic effect of many anticancer drugs relies on their ability to damage DNA. Drug resistance can be associated with the ability to remove potentially lethal DNA lesions. DNA damage tolerance offers an alternative route to resistance. In a drug-tolerant cell, persistent DNA damage has become uncoupled from cell death. Tolerance to some DNA damaging drugs is accompanied by...