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Biomedical subjects

R E Tarone

Publications and source records attributed to R E Tarone.

At least 163 records · Page 9Linked to original sources
PubMed1979

Statistical issues in interpretation of chronic bioassay tests for carcinogenicity.

The interpretation of chronic bioassay tests for carcinogenicity requires that the data be appropriately recorded. A "case history" for each animal links the pathology data for each organ of each animal to the length of its life. This information can be used in interpretation of the tumor incidences in light of the survival information. The role of historical controls was discussed, and the use of significance tests in a multidisciplinary approach to the assessment of the pattern of tumor response was suggested. Multiple comparison methods valid for the interpretation of continuous (or measurement) data do not apply to the discrete data analyses used in these studies. The ideas and methods of these studies were applied to an animal study of chloroform.

Animals↗
PubMed1979

Increased susceptibility of mouse cells to fluorescent light-induced chromosome damage after long-term culture and malignant transformation.

Exposure of mouse cells in culture to fluorescent light has been shown to produce chromatid breaks and exchanges. Hydrogen peroxide formed in the cell during illumination has been implicated as the causative agent. The present results indicate that susceptibility to light-induced chromosome damage increases with time in culture and seems to be associated with or requisite for the spontaneous malignant transformation of mouse cells. All three cell lines followed during long-term culture that either became tumorigenic or showed cytological evidence of neoplastic transformation developed a concomitant increase in susceptibility. In three additional cell lines, susceptibility to light-induced chromatid damage was significantly increased in the spontaneously transformed malignant cells as compared with their nonneoplastic precursors. The increased susceptibility is not simply the result of long-term culture, since three other nonneoplastic cell lines after prolonged culture were significantly less susceptible than their malignant counterparts. Increased susceptibility to light-induced chromatid damage could result from impaired DNA repair or from the loss of defense mechanisms for destroying H2O2 or scavenging free radicals.

Animals↗
PubMed1978

Fluorescent light-induced chromosome damage and its prevention in mouse cells in culture.

Twenty-hour-exposure to fluorescent light produces chromatid breaks in a line of adult mouse lung cells grown in Dulbecco-Vogt medium supplemented with fetal bovine serum. The light-induced damage appears to be enhanced by increasing the concentration of oxygen in the gas phase of the culture. The effective wavelength(s) of light is in the visible range between 400 and 450 nm andis probably the mercury emission peak at 405 or 436 nm. Addition of catalase or glutathione with ascorbic acid to the culture medium reduced the number of chromatid breaks to a level not significantly different from that in the shielded cultures. It thus appears that the production of H2O2 in the culture medium or in the cell is responsible for the chromatid breaks. Most of the chromosomal abnormalities observed in long-term culture of mouse cells may result from exposure of cells or medium to fluorescent room lights in the presence of atmospheric oxygen. These genetic abnormalities can be minimized by shielding cells and medium from light, lowering the PO2 of the medium, and including reducing agents such as glutathione and ascorbic acid in the medium formulation.

Ascorbic Acid↗
PubMed1978

Fluorescent light-induced DNA crosslinkage and chromatid breaks in mouse cells in culture.

A single 20-hr exposure of mouse cells derived from embryonic or lung tissue to cool-white fluorescent light (4.6 W/m2) causes both DNA damage and chromosome aberrations including chromatid breaks, exchanges, and minutes. In Kohn's alkaline elution technique, the DNA from exposed cells elutes more slowly than that from shielded cells. Because larger molecular weight DNA elutes slower than smaller, we interpret these results to mean that the DNA in cells exposed to light is crosslinked. The estimated frequency of crosslinks is sufficient to account for the number of chromatid breaks observed. The types of chromosome aberrations produced by light indicate that the primary lesion results in chromatid rather than chromosome breaks, and the results suggest an influence of cell density in that cells in densely populated cultures showed few or no chromatid breaks after irradiation. The present results, together with observations from the literature, suggest that the DNA crosslinkage and the chromosome aberrations produced by light may be related.

Cells, Cultured↗
PubMed1977

The cytology of spontaneous neoplastic transformation in culture.

Thirteen cell lines derived from embryos of the mouse, rat and hamster were sampled at closely spaced intervals for cytology and spontaneous neoplastic transformation. Transformation, determined by growth of the cells as malignant neoplasms in compatible hosts, occurred in eight lines and appeared to be unrelated to time in culture, passage number, proliferative activity of the cells or type of serum used to supplement the culture medium. In an effort to establish cytologic criteria for malignancy of rodent fibroblasts, cultures were examined for 19 cytologic abnormalities. The percentage of cells or colonies showing each of the abnormal properties was recorded. Five of the 19 were found to correlate with neoplastic transformation in all cell lines. These were cytoplasmic basophilia, reduced cytoplasmic spreading on substrate, cording, high nuclear: cytoplasmic ratio and clumping. Each of these properties is amenable to quantitation or computerized image analysis. On the basis of the five cytologic criteria, the percentage of colonies diagnosed neoplastic, borderline and non-neoplastic was determined for each line. Although these percentages varied from one transplant generation to another, the percentage of neoplastic colonies tended to increase with time in all lines which became malignant, and the borderline colonies tended to decrease, suggesting a progression from borderline to neoplastic state.

Animals↗
PubMed1977

Topography of nonneoplastic and neoplastic cells of common origin.

The possibility that neoplastic transformation may characteristically alter cell surface morphology prompted a comparison by scanning electron microscopy of nonneoplastic and tumorigenic cell lines from a single clone of mouse embryo cells. Among those studied by scanning electron microscopy, six lines of this clone proved nonneoplastic, and nine others underwent neoplastic transformation in culture, as evidenced by tumor production in vivo. Combined cinephotomicrography and scanning electron microscopy allowed the determination of postmitotic time and topography of individual cells without perturbing the cells or detectably altering their surface morphology; no pattern of morphological change as a function of postmitotic time was evident in either nonneoplastic or neoplastic cell populations. Accordingly, these cell populations could be compared under their usual conditions of attached asynchronous growth despite differences in proliferation rates. Cells of the neoplastic lines were characteristically less spread, and some lines displayed greater morphological variability than was evident among cells of nonneoplastic lines. However, most cells in all nine neoplastic lines and all six nonneoplastic lines were smooth surfaced. Thus, the exaggerated incidence of microvilli, ruffles, or blebs reported for established tumor-derived lines and most morphologically transformed lines did not prove a reliable criterion of neoplastic state for these cell lines of common origin grown under the same culture conditions.

Animals↗
PubMed1977

Morphometric analysis of neoplastic transformation in rodent fibroblast cell lines.

Populations from seven pairs of neoplastic and nonneoplastic cell lines of common origin were compared for evidence of a change in morphotogical parameters accompanying neoplastic transformation. Projected cytoplasmic area, projected nuclear area, cell dry mass, nuclear dry mass, whole-cell absorption at 265 nm, and nuclear absorption at 265 nm were determined. Neoplastic transformation was consistently accompanied by three morphological features: (a) decrease in projected area of the lamellar cytoplasm; (b) decrease in the projected area of the nucleus; and (c) decrease in dry mass of the lamellar cytoplasm. Ultraviolet absorption was generally less in the neoplastic cells than in the nonneoplastic cells, while nuclear mass remained approximately the same. These results are interpreted as quantitative evidence that neoplastic transformation is accompanied by morphological change. The morphological events may be characterized as a loss in cell surface and nuclear membrane components.

Cell Division↗
PubMed1977

False-positive and false-negative rates for carcinogenicity screens.

The implementation of a number of chemical carcinogen screening programs has been accompanied by the observation that some screens might have high false-positive error rates. With designs presently used at the National Cancer Institute and historical spontaneous tumor rates based upon control animals in previous experiments, we compute upper bounds on the false-positive error rates for several screening strategies. False-positive results are much less likely to occur at tissue sites with low spontaneous tumor rates; hence the site at which a significant tumor increase occurs is important. There is danger in relying solely upon the finding of statistical significance without incorporating biological knowledge and corroborative evidence such as the presence of a dose-response relationship or experimentally consistent results in different species or sexes. A report by the National Cancer Institute Carcinogenesis Program demonstrates these concepts.

Animals↗
PubMedDate not supplied

Breast cancer trends of black women compared with white women.

OBJECTIVE: To investigate why breast cancer mortality rates have decreased in the 1990's for white women but not for black women. DESIGN: Racial differences in breast cancer incidence, survival, and mortality rates were examined using regression methods and age-period-cohort models. SETTING: United States breast cancer mortality rates from 1970 through 1995, breast cancer incidence rates from 1980 through 1995, and 3-year survival rates from 1980 through 1993. The incidence and survival data are from the Surveillance, Epidemiology, and End Results Program, representing 11% of the US population, of the National Cancer Institute, Bethesda, Md. RESULTS: For both white and black women aged 30 to 39 years, breast cancer mortality rates began decreasing in 1987. For white women aged 40 to 79 years, breast cancer mortality rates declined after 1989, and for black women aged 40 to 69 years, mortality rates ceased increasing in the middle to late 1980s. Birth cohort trends were similar by race, but calendar period trends and survival rates differed. CONCLUSIONS: Declines in mortality rates in women younger than 40 years reflect a favorable birth cohort trend for women born after 1948 and likely reflect changes in risk factors. The increased early detection of breast cancer by mammography and improvements in breast cancer treatment appear to be contributing to the improving mortality trends in older women, although black women appear to have benefited less than white women from early detection and treatment advances. In addition, substantial increases in survival rates for white women with regional disease have contributed to their declining mortality rates and likely reflect an increasing use of beneficial adjuvant therapy.

Adult↗
PubMedDate not supplied

Hypersensitivity to ionizing radiation in cultured cells from Down syndrome patients.

Down syndrome is caused by trisomy of chromosome 21 and is comprised of a constellation of abnormalities including neuropathological features that closely resemble those characterizing the neurodegeneration of Alzheimer disease. Because cultured cell lines from patients with Alzheimer disease and other neurodegenerations have a hypersensitivity to the lethal effects of DNA-damaging agents, we studied the response of Down syndrome lymphoblastoid lines to the lethal effects of ionizing and ultraviolet radiation. Lines from the four Down syndrome patients were more sensitive to X-rays than lines from 28 normal donors (P = 10(-4)), while survival of the Down syndrome lines after ultraviolet irradiation was not significantly different from normal. This hypersensitivity to X-rays, which may reflect defective repair of X-ray-induced DNA damage, represents the first abnormality common to cultured cells from both Down syndrome and Alzheimer disease patients.

Alzheimer Disease↗
PubMedDate not supplied

Alzheimer disease fibroblasts are hypersensitive to the lethal effects of a DNA-damaging chemical.

A group of fibroblast lines from three patients with the sporadic form of Alzheimer disease (AD) showed a small but statistically significant hypersensitivity to the lethal effects of the DNA-damaging chemical N-methyl-N'-nitro-nitrosoguanidine (MNNG) when compared with lines from eight normal control subjects. A fibroblast line from a patient with a dominantly inherited form of familial AD had a hypersensitivity similar to that of the three sporadic AD lines. However, fibroblast lines from a group of five patients with spinal muscular atrophy (SMA) were not hypersensitive to the chemical, demonstrating that not every primary neuronal degeneration manifests hypersensitivity to this chemical. These findings are consistent with the possibility that a defect in DNA-repair mechanisms may be the cause of the in vitro hypersensitivity, as well as the premature death of neurons in vivo, in both the sporadic and familial forms of AD.

Alzheimer Disease↗
PubMedDate not supplied

Ingested asbestos and intestinal carcinogenesis in F344 rats.

The effect of oral exposure to amosite or chrysotile on azoxymethane-induced intestinal carcinogenesis was investigated in male F344 rats. In two separate experiments, F344 rats, 6 weeks of age, were given ten weekly subcutaneous injections of azoxymethane, and intragastric administration of amosite or chrysotile three times weekly during this period. In experiment 1, rats were sacrificed at 34 weeks. The incidence rates and mean number of intestinal tumors per rat were similar in all groups. However, a slightly higher incidence, not significant, of metastatic intestinal carcinomas was seen in rats exposed to asbestos. In the second experiment, rats were allowed to live out their life span. The incidence of intestinal tumors was similar in the rats receiving amosite with azoxymethane and azoxymethane alone. Thirty-two percent of the rats receiving amosite alone had colon tumors; these tumors are usually rare in F344 rats. It was concluded that the experimental evidence suggested but did not prove that oral asbestos exposure in F344 rats may have increased the incidence of intestinal tumors occurring naturally.

Animals↗