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Biomedical subjects

J C Barrett

Publications and source records attributed to J C Barrett.

At least 379 records · Page 21Linked to original sources
PubMed1978

Neoplastic transformation induced by a direct perturbation of DNA.

Treatment of Syrian hamster embryo cells with 5-bromodeoxyuridine followed by near ultraviolet irradiation results in neoplastic transformation of these cells. This demonstrates that a direct perturbation of DNA is sufficient to initiate neoplastic transformation.

Bromodeoxyuridine↗
PubMed1978

Induction of 6-thioguanine- and ouabain-resistant mutations in synchronized Syrian hamster cell cultures during different periods of the S phase.

Cells of a transformed Syrian hamster line, BP6T, were synchronized by a period of growth in low serum with a subsequent blockage of the cells at the G1/S boundary by hydroxyurea. This method provided cells with nearly 100% synchrony, although approximately 20% of the cells were non-cycling. The cells were then treated with 10(-5) M 5-bromodeoxyuridine for 1 of 5 1-h periods during the S phase and subsequently irradiated with near-ultraviolet light for 5 min. The BrdU plus irradiation treatment induced 6-thioguanine- and ouabain-resistant mutants while BrdU alone or irradiation alone was not mutagenic. 6-Thioguanine-resistant mutants were induced only during early S phase by BrdU plus irradiation treatment. Ouabain-resistant mutants, however, were induced in a biphasic pattern, during early S phase and also during late S phase. The induction of ouabain-resistant mutants at two distinct periods of S phase suggests the presence of two loci for the gene(s) of Na+/K+ ATPase.

Cell Cycle↗
PubMed1978

Relationship between somatic mutation and neoplastic transformation.

Somatic mutation and neoplastic transformation of diploid Syrian hamster embryo cells were examined concomitantly. Mutations induced by benzo[a]pyrene and N-methyl-N'-nitro-N-nitrosoguanidine were quantitated at the hypoxanthine phosphoribosyltransferase and Na(+)/K(+) ATPase loci and compared to phenotypic transformations measured by changes in cellular morphology and colony formation in agar. Both cellular transformations had characteristics distinct from the somatic mutations observed at the two loci. Morphological transformation was observed after a time comparable to that of somatic mutation but at a frequency that was 25- to 540-fold higher. Transformants capable of colony formation in agar were detected at a frequency of 10(-5)-10(-6), but not until 32-75 population doublings after carcinogen treatment. Although this frequency of transformation is comparable to that of somatic mutation, the detection time required is much longer than the optimal expression time of conventionally studied somatic mutations. Neoplastic transformation of hamster embryo cells has been described as a multistep, progressive process. Various phenotypic transformations of cells after carcinogen treatment may represent different stages in this progressive transformation. The results are discussed in this context and the role of mutagenesis in the transition between various stages is considered. Neoplastic transformation may be initiated by a mutational change, but it cannot be described completely by a single gene mutational event involving a dominant, codominant, or X-linked recessive locus. Neoplastic transformation induced by chemical carcinogens is more complex than a single gene mutational process. Thus, this comparative study does not give experimental support to predictions of the carcinogenic potential of chemicals based on a simple extrapolation of the results obtained from conventional somatic mutation assays.

Adenosine Triphosphatases↗
PubMed1978

Evidence for the progressive nature of neoplastic transformation in vitro.

The temporal acquisition of in vitro phenotypes associated with neoplasia were examined after exposure of Syrian hamster embryo cells to a chemical carcinogen. Quantitative assays measuring morphological changes, enhanced fibrinolytic activity, and anchorage independent growth were used to detect the development of transformed cells within a population of normal hamster embryo cells. Morphological transformation and enhanced fibrinolytic activity were early changes observed after treatment with benzo[alpha]-pyrene, whereas the ability to grow in semisolid agar was delayed 32-75 population doublings after carcinogen exposure. This delay was not due to selection of a small number of cells that were present early after treatment but at a level below detection, because a large percentage of the cells isolated at early passage (10(3)-fold above the level of detection) developed the potential for anchorage independent growth at later passages. This development of the anchorage independent growth phenotype was induced by the carcinogen treatment, because spontaneous transformation was rare. These observation suggest that multiple cellular changes are required for the acquisition of the capacity for anchorage independent growth and that neoplastic transformation in vitro is a progressive process through qualitatively different stages. Thus, an analogy can be drawn to the progressive nature of in vivo carcinogenesis. These results strongly justify the study of oncogenesis in cell culture as a model for neoplastic transformation in vivo.

Animals↗
PubMed1978

The redundant factor method and bladder cancer mortality.

Of the three factors, age at death, epoch of death, and epoch of birth, one seems almost superfluous. It may nevertheless be worthwhile to include all three in a mortality analysis, allowing for the constraints that the redundancy imposes. This procedure is applied to data for England and Wales on bladder cancer mortality from 1951 to 1970.

Adult↗
PubMed1978

Effects of various factors on selection for family planning status and natural fecundability: a simulation study.

The effect of various factors on selection for family planning status and for natural fecundability is studied in a simulation that incorporates a beta distribution of fecundability among women. The mean fecundabilities of current spacers, current limiters, current nonusers, and pregnant women are compared. These ratios are influenced by duration of marriage and by desired number of children. Effects of different levels of contraception are measured. Another strategy, spacing the last two wanted births, is also studied. It is found that breast-feeding status has little effect on fecundability selection. The women usually found to have greatest fecundability are not those recently pregnant at durations of marriage five and ten years, unless they wanted fewer than two children, but rather those who are using contraception to limit the number of children.

Adult↗
PubMed1978

A method of mortality analysis: application to breast cancer.

A regression analysis of mortality can benefit from the introduction of certain apparently redundant factors. Following a description of the method of calculating the regression coefficients, data on mortality from breast cancer in England and Wales for 1951-1970 are analysed as a function of age group, quinquennium of birth and quinquennium of death.

Age Factors↗
PubMed1977

Quantitation of fibrinolytic activity of Syrian hamster fibroblasts using 3H-labeled fibrinogen prepared by reductive alkylation.

Tritium-labeled fibrinogen with a specific activity of 2.0 X 10(7) cpm/mg was prepared by the method of reductive alkylation. The use of the 3H-fibrinogen as a substrate for detection of both intracellular and extracellular fibrinolytic activity derived from cultures of benzo(a)pyrene-transformed Syrian hamster cell lines was examined in cell-free assays, 3H-fibrinogen enabled reliable quantitation of the fibrinolytic activity associated with neoplastic cells. The elevated extracellular fibrinolytic activity in the transformed cell lines as compared to normal hamster embryo cultures was demonstrated with this substrate. The ease with which large quantities of 3H-fibrinogen of high specific activity and prolonged half-life can be prepared makes the use of this substrate an attractive alternative to 125I-labeled fibrinogen.

Alkylation↗
PubMed1977

Temporal acquistion of enhanced fibrinolytic activity by syrian hamster embryo cells following treatment with benzo(a)pyrene.

Following treatment of Syrian hamster embryo cells with benzo(a)pyrene, the time required for the expression of enhanced fibrinolytic activity was examined. For this study, the fibrin-agarose overlay method was developed to distinguish the activity of normal and transformed colonies of hamster cells. Colonies possessing enhanced fibrinolytic activity were not observed one passage (2 weeks after treatment). Morphologically transformed colonies, which exhibited no enhanced fibrinolytic activity, were observed 8 days following treatment. In contrast to these two early changes, cells capable of growth in soft agar were observed much later (6 to 8 weeks after treatment). Untreated Syrian hamster embryo cells generally senesced and did not exhibit enhanced fibrinolytic activity. Approximately 1 of 10 untreated cultures escaped senescence and evolved as a continuous cell line; such cultures frequently exhibited enhanced fibrinolytic activity. These results suggest that the acquisition of enhanced fibrinolytic activity, while perhaps not a cause of neoplastic transformation, may reflect a loss of control of the normal function of the cellular genetic apparatus during the process of transformation.

Benzopyrenes↗
PubMed1975

A circulating renin activator in essential hypertension.

The rate of angiotensin generation with added renin in plasma from patients with benign essential hypertension has been shown to be higher than in plasma from norm ensive controls. An index of the angiotensin generation rate in relation to to al plasma renin substrate (PRS-r index) has been defined which allows for screening for "activated" plasma. In hypertensive subjects, this index was shown to be higher than that of the normotensive subjects (61 plus or minus 2.4 SE, and 45 plus or minus 5 SE). The index did not correlate with the absolute levels of blood pressure, 24-hour sodium excretion, or plasma renin activity in hypertensive subjects either during the control period or during acute alterations of blood pressure, but was shown to respond in a parallel fashion with chronically induced changes in blood pressure and circulating levels of angiotensin I. By the use of an isolated system of human renin and homologous renin substrate, we have demonstrated that plasma from hypertensive subjects contains a modifier of the renin reaction which increases both V-max and Km of the system, behaving as an uncompetitive activator. No significant change was noted with the addition of normal plasma to the same isolated system.

Angiotensin II↗