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Biomedical subjects

J C Barrett

Publications and source records attributed to J C Barrett.

At least 397 records · Page 22Linked to original sources
PubMed1973

Age, time and cohort factors in mortality from cancer of the cervix.

Data for mortality from cancer of the cervix in England and Wales by 5-year age groups and four quinquennia (1951-70) are analysed. The logarithms of the mortality rates are regressed on age group, epoch of death and epoch of birth. The factors obtained are considered in relation to particular features of the mortality pattern, such as the reversal of trend in certain age groups.

Adult↗
PubMedDate not supplied

Mechanisms of arsenic-induced cell transformation.

Arsenic is a well-established carcinogen in humans, but there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promoter in two-stage models of carcinogenicity in mice. Studies with cells in culture have provided some possible mechanisms by which arsenic and arsenical compounds may exert a carcinogenic activity. Sodium arsenite and sodium arsenate were observed to induce morphological transformation of Syrian hamster embryo cells in a dose-dependent manner. The trivalent sodium arsenite was greater than tenfold more potent than the pentavalent sodium arsenate. The compounds also exhibited toxicity; however, transformation was observed at nontoxic as well as toxic doses. At low doses, enhanced colony forming efficiency of the cells was observed. To understand the mechanism of arsenic-induced transformation, the genetic effects of the two arsenicals were examined over the same doses that induced transformation. No arsenic-induced gene mutations were detected at two genetic loci. However, cell transformation and cytogenetic effects, including endoreduplication, chromosome aberrations, and sister chromatid exchanges, were induced by the arsenicals with similar dose responses. These results support a possible role for chromosomal changes in arsenic-induced transformation. The two arsenic salts also induced another form of mutation-gene amplification. Both sodium arsenite and sodium arsenate induced a high frequency of methotrexate-resistant 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Induction by modified purines (2-aminopurine and 6-N-hydroxylaminopurine) of chromosome aberrations and aneuploidy in Syrian hamster embryo cells.

The modified purines, 2-aminopurine and 6-N-hydroxylaminopurine, are known point mutagens in prokaryotic organisms. 2-Aminopurine is much less potent than 6-N-hydroxylaminopurine in inducing gene mutation in mammalian cells in culture and this corresponds to the relative activity of these two compounds in inducing tumors in rats and neoplastic transformation of Syrian hamster embryo cells in culture. We report here that these modified purines can induce chromosome aberrations, including chromatid gaps, breaks, and exchanges, as well as numerical chromosome changes in Syrian hamster embryo cells. These chromosome mutations occur over the concentration range of chemical needed to induced morphological transformation of the same cells. It is not known how nucleic base analogs induce chromosome mutations; however, this activity must be considered in attempting to understand the mechanism by which these agents induce neoplastic transformation of cells.

2-Aminopurine↗
PubMedDate not supplied

Mechanisms of multistep carcinogenesis: keys to developing in vitro approaches for assessing the carcinogenicity of chemicals.

The process of neoplastic development is a complex combination of genetic and non-genetic changes within a tissue. It is, therefore, not surprising that a number of mechanisms exist by which chemicals influence this process. In designing short-term tests to detect potential carcinogens, the major emphasis to date has been on genetic assays. This is justified on both theoretical and practical grounds. Substantial evidence exists to support the hypothesis that genetic damage increases the probability of tumour development. Mutational assays for gene mutations, clastogenicity and aneuploidy induction are therefore extremely important tests for carcinogens. Unfortunately, few assays exist for detecting chemicals that induce gene amplification, and thus, if these are carcinogens that specifically induce this type of genetic change, they may go undetected. Because of a variety of possible differences between a chemical's activity in vivo and in vitro, it is to be expected that chemicals that are mutagenic in vitro may not have a significant carcinogenic effect in vivo. However, the potential harm of these chemicals to man does exist and may be expressed under different conditions (e.g. species- or organ-specific carcinogenic effects) or as non-carcinogenic hazards.

Animals↗
PubMedDate not supplied

Nonrandom loss of chromosome 15 in Syrian hamster tumours induced by v-Ha-ras plus v-myc oncogenes.

Nonrandom chromosome rearrangements, observed in a variety of human and animal tumours, are associated in some cases with enhanced expression or deregulation of cellular oncogenes. Recently, it was shown that normal, diploid rodent cells are neoplastically transformed following transfection with two cooperating oncogenes, for example myc plus ras. However, the number of steps necessary to convert a normal cell into a malignant cell is unknown. If activation of two oncogenes is sufficient for tumorigenicity, tumours derived from diploid cells transformed by the transfected oncogenes may remain diploid or have only random chromosome alterations. We have performed cytogenetic analyses of tumours formed after transfection of Syrian hamster embryo cells with either v-Ha-ras plus v-myc DNAs or polyoma DNA alone. Whereas polyoma-induced, tumour-derived cells were diploid, tumours induced by v-Ha-ras plus v-myc oncogenes were monoclonal and had a nonrandom chromosome change, monosomy of chromosome 15. Thus, an additional change, loss of chromosome 15, is required for or is advantageous for tumorigenicity induced by v-Ha-ras plus v-myc oncogenes. These results suggest that the neoplastic progression of normal, diploid cells requires more than two steps under certain conditions.

Animals↗
PubMedDate not supplied

Insulin-like growth factor-1 inscribes a gene expression profile for angiogenic factors and cancer progression in breast epithelial cells.

Activation of the insulin-like growth factor-1 receptor (IGF-1R) by IGF-1 is associated with the risk and progression of many types of cancer, although despite this it remains unclear how activated IGF-1R contributes to cancer progression. In this study, gene expression changes elicited by IGF-1 were profiled in breast epithelial cells. We noted that many genes are functionally linked to cancer progression and angiogenesis. To validate some of the changes observed, the RNA and/or protein was confirmed for c-fos, cytochrome P450 1A1, cytochrome P450 1B1, interleukin-1 beta, fas ligand, vascular endothelial growth factor, and urokinase plasminogen activator. Nuclear proteins were also temporally monitored to address how gene expression changes were regulated. We found that IGF-1 stimulated the nuclear translocation of phosphorylated AKT, hypoxic-inducible factor-1 alpha, and phosphorylated cAMP-responsive element-binding protein, which correlated with temporal changes in gene expression. Next, the promoter regions of IGF-1-regulated genes were searched in silico. The promoters of genes that clustered together had similar regulatory regions. In summary, IGF-1 inscribes a gene expression profile relevant to cancer progression, and this study provides insight into the mechanism(s) whereby some of these changes occur.

Blotting, Western↗
PubMedDate not supplied

Managing asthma within the context of the rural family.

The purpose of this qualitative study was to describe the experiences of rural families caring for children with asthma. The chief caregivers from six rural families were interviewed about the family's daily experiences in living with asthma, their knowledge of asthma triggers, and strategies for managing asthma. Parental knowledge about asthma and asthma management strategies was quite good. The cost of asthma regimens and school policies about medications were major barriers to better control. Other management strategies were directed at maintaining normality of family life.

Adult↗