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Biomedical subjects

R E Tarone

Publications and source records attributed to R E Tarone.

At least 19 recordsLinked to original sources
PubMed1992

Implications of birth cohort patterns in interpreting trends in breast cancer rates.

BACKGROUND: Most investigations of trends in cancer rates are based on a cross-sectional approach, i.e., an examination of trends in rates by year of diagnosis or death. When there are longitudinal effects (i.e., trends in rates with successive birth cohorts), interpretation of cross-sectional trends can be misleading. Based on cross-sectional comparisons, U.S. breast cancer mortality rates have been reported to be decreasing over the last 20 years in younger women but to be increasing during the same period in older women. PURPOSE: To examine the impact of longitudinal effects on the divergence of cross-sectional trends in breast cancer mortality with age, we examined breast cancer mortality rates from 1969 to 1988 by birth cohort for White women in the United States. METHODS: By using a novel, nonparametric, permutational method to analyze 2-year, age-specific mortality rates for women aged 30-89 years, we identified trends in rates with successive birth cohorts. RESULTS: The divergence in trends with age is shown to be consistent with an increase in breast cancer risk with successive birth cohorts from 1900 to 1916 and with a decrease in breast cancer risk with successive birth cohorts beginning around 1926. CONCLUSION: Longitudinal effects have a significant impact on cross-sectional trends in breast cancer mortality. IMPLICATIONS: Continuation of the birth cohort trend in younger women, which could correspond to changes in reproductive patterns accompanying the "baby boom," would result in decreasing cross-sectional trends in women 60-69 years of age over the next decade and in women 70-79 years of age in the subsequent decade. Longitudinal effects must be taken into consideration when monitoring and evaluating the effects of early detection, treatment, and intervention programs using national rates.

Adult↗
PubMed1992

Skin cancer and chromosomal aberrations induced by ultraviolet radiation. Evidence for lack of correlation in xeroderma pigmentosum variant and group E patients.

Ultraviolet radiation (UV) in sunlight induces an abnormally high incidence of skin cancer in patients with xeroderma pigmentosum (XP), an autosomal recessive disease with defects in the repair of damaged DNA. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblast lines from a patient with the variant form of XP, from a patient with the complementation group E form, and from two patients with the complementation group C form. In contrast to results with patients having other forms of XP, the group E and variant patients showed no abnormal increase in UV-induced chromosomal aberrations. Even in the presence of caffeine, which exacerbates the postreplication repair defect of UV-irradiated XP variant cells, there was still no abnormally elevated frequency of UV-induced chromosomal aberrations in the variant cells. These results, indicating that the level of UV-induced chromosomal aberrations is not correlated with these patients' marked susceptibility to skin cancer, suggests that some mechanism other than genetic transposition is causatively related to these XP patients' high incidence of sunlight-induced skin cancer.

Caffeine↗
PubMed1992

Retinoid protection against x-ray-induced chromatid damage in human peripheral blood lymphocytes.

Oral administration of isotretinoin (13-cis retinoic acid) was shown previously (Kraemer, K. H., J. J. DiGiovanna, A. N. Moshell, R. E. Tarone, and G. L. Peck. 1988. N. Engl. J. Med. 318:1633-1637) to reduce the frequency of skin cancers in xeroderma pigmentosum (XP) patients. The mechanism of protection was unclear. In the present study, x-ray-induced chromatid damage in PHA-stimulated blood lymphocytes from five XP patients receiving isotretinoin was approximately half that in blood samples from the same patients before or subsequent to treatment. The x-ray-induced chromatid damage in blood lymphocytes from a normal control was reduced significantly by cocultivation with blood or plasma from an XP patient receiving isotretinoin or by addition of 10(-6) M isotretinoin to cultures 1 h before x-irradiation. A similar reduction in x-ray-induced chromatid damage was reported previously by adding to the culture medium, mannitol, a scavenger of the free hydroxyl radical, or catalase, which decomposes hydrogen peroxide; both of these products are generated during ionizing radiation. The present observations suggest that isotretinoin acts as a scavenger of such radiation products, thereby providing protection against x-ray-induced chromatid damage.

Adult↗
PubMed1991

Case-control study of canine malignant lymphoma: positive association with dog owner's use of 2,4-dichlorophenoxyacetic acid herbicides.

A hospital-based case-control study of companion dogs examined the risk of developing canine malignant lymphoma associated with the use of chemicals in and about the home. Information from a self-administered owner questionnaire and/or a telephone interview of about 491 cases, 466 nontumor controls, and 479 tumor controls indicated that owners in households with dogs that developed malignant lymphoma applied 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides to their lawn and/or employed commercial lawn care companies to treat their yard significantly more frequently than control owners (odds ratio = 1.3). In addition, the risk of canine malignant lymphoma rose to a twofold excess with four or more yearly owner applications of 2,4-D. The findings in this study are consistent with occupational studies in humans, which have reported modest associations between agricultural exposure to 2,4-D and increased risk of non-Hodgkin's lymphoma, the histology and epidemiology of which are similar to those of canine malignant lymphoma. The present study suggests that human health implications of 2,4-D exposure in the home environment should receive further investigation.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1991

Radiation-induced chromatid aberrations in Cockayne syndrome and xeroderma pigmentosum group C fibroblasts in relation to cancer predisposition.

We showed previously that the persistence of chromatid breaks and gaps after G2 phase irradiation with X-rays or near-UV visible light characterizes skin fibroblasts from individuals with cancer-prone genetic diseases. This abnormal response appears to result from deficient DNA repair during G2 and to be associated with cancer proneness. We have, therefore, compared the responses of cells from two genetic disorders, Cockayne syndrome (CS) and xeroderma pigmentosum complementation group C(XP-C), both of which exhibit cellular hypersensitivity to sunlight, but only one of which, XP, manifests a high rate of sunlight-induced cancer. CS cells, in contrast to XP cells, showed a normal G2 response to irradiation with either X-rays or near-UV visible light. However, CS cells showed a deficiency in repair of DNA damage inflicted by light during S and G1 phases of the cell cycle. The present results support the concept that deficient DNA repair during G2 phase plays a role in carcinogenesis. This deficient repair in the presence of DNA damage and continuous cell cycling from activation of proto-oncogenes or loss of suppressor genes may be necessary and sufficient for cancer development.

Causality↗
PubMed1991

Evidence for defective repair of cyclobutane pyrimidine dimers with normal repair of other DNA photoproducts in a transcriptionally active gene transfected into Cockayne syndrome cells.

Cockayne syndrome (CS) and xeroderma pigmentosum (XP), autosomal recessive diseases with clinical and cellular hypersensitivity to UV radiation, differ in ability to repair UV DNA photoproducts in their overall genome: normal repair in CS, defective repair in XP. In order to characterize a DNA repair defect in an active gene in CS, we measured the capacity of cells from patients with CS and XP to reactivate 2 major types of UV-induced DNA damage, photoreactivatable (i.e., cyclobutane pyrimidine dimers) and non-photoreactivatable (primarily pyrimidine-(6-4)pyrimidone photoproducts), in the actively transcribing chloramphenicol acetyltransferase (cat) gene of the plasmid expression vector pRSV-cat. Epstein-Barr virus-transformed lymphoblast lines from 4 normal persons and from 3 patients with CS and from two with XP were transiently transfected with the plasmid, and the cat activity in cell extracts was determined. When the cells were transfected with UV-irradiated plasmid, expression was abnormally decreased in both the CS and XP cells. When the cyclobutane pyrimidine dimers in the UV-irradiated plasmid were removed by photoreactivation prior to transfection, cat expression in the CS, but not in the XP, lines reached normal levels. These data imply that both the XP and CS cells are unable to repair normally the cyclobutane pyrimidine dimer photoproducts which block transcription of cat. However, the CS, but not XP, cells can repair normally the other UV-induced photoproducts which block transcription. The ability of CS, but not XP, cells to repair these non-dimer photoproducts indicates that the active gene repair mechanism treats the cyclobutane pyrimidine dimer differently from the non-dimer photoproducts.

Cell Line↗
PubMed1990

Excess of seminomas observed in Vietnam service U.S. military working dogs.

During the Vietnam War, US military working dogs served with their companion dog handlers in close proximity, sharing common exposures to war-related activity, many zoonotic infectious agents, chemical pesticides, phenoxy herbicides, and extensive use of therapeutic drugs. To gain insight into the effects of the Vietnam experience, we investigated the occurrence of neoplasms in military working dogs based on standard necropsy examination by the Armed Forces Institute of Pathology. We observed that these dogs experienced significant elevated risks for testicular seminoma and, independently, testicular dysfunction. Experimental evidence shows testicular dysfunction and impaired spermatogenesis in laboratory animals exposed to phenoxy herbicides, dioxin, or tetracycline, and antibiotic used extensively in military working dogs in Vietnam. Because an unexplained significant decrease in sperm quality in Vietnam veterans has been observed by the Centers for Disease Control, further research is warranted if we are to clarify military service in Vietnam as a risk factor for testicular dysfunction. The testis should be made a priority site in the study of Vietnam experience-related cancers.

Animals↗
PubMed1990

Enhanced chromatid damage in blood lymphocytes after G2 phase x irradiation, a marker of the ataxia-telangiectasia gene.

An assay for ataxia-telangiectasia (A-T) heterozygotes, i.e., healthy carriers of the A-T gene(s), requiring only a small sample (3.5 mL) of peripheral blood, is described. Frequencies of chromatid aberrations in phytohemagglutinin-stimulated blood lymphocytes collected by demecolcine from 0.5 hour to 1.5 hours after x irradiation with 58 roentgens were twofold to threefold higher in A-T heterozygotes than in clinically normal controls and twofold to three-fold higher in A-T patients (homozygotes) than in A-T gene carriers. The persistence of chromatid breaks and gaps in lymphocytes following radiation-induced DNA damage during G2 suggests a deficiency or deficiencies in DNA repair that may be the defect at the molecular level that results in the enhanced radiosensitivity and cancer proneness characterizing A-T gene carriers and patients.

Adolescent↗
PubMed1990

Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia.

The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.

China↗
PubMed1990

Enhanced malignant conversion of benign mouse skin tumors by cisplatin.

The chemotherapeutic agent cisplatin, reported to be a complete carcinogen in rodents and a tumor initiator for mouse skin, was tested for activity to enhance the conversion of carcinogen-induced skin papillomas to carcinomas. Initiation of mouse skin by 7,12-dimethylbenz[a]anthracene followed by 12 weeks of promotion by 12-O-tetradecanoylphorbol-13-acetate produced seven to eight papillomas/mouse. Ten weekly injections of 100 micrograms of cisplatin into these papilloma-bearing mice induced a 2.3-fold enhancement of conversion relative to the spontaneous rate of 1.9%. Even a single exposure to cisplatin in tumor-bearing mice increased the carcinoma incidence to the same extent as 10 exposures to urethane, an agent previously shown to enhance malignant conversion. At the dose tested, cisplatin was inactive as a complete carcinogen or a tumor promoter. Cisplatin-DNA adducts, measured in samples from skin, liver, and kidneys, were persistent for at least 4 weeks after the last exposure to cisplatin. Thus cisplatin is a relatively potent inducer of the putative genotoxic changes required for conversion of skin tumors from a benign to a malignant phenotype. The activity of cisplatin in the initiation and malignant conversion stages in this animal model for carcinogenesis suggests that patients given cisplatin-based chemotherapy are at increased risk for the development of treatment-induced second cancers.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Persistence of chromatid damage after G2 phase X-irradiation in lymphoblastoid cells from Gardner's syndrome.

Previous reports showed that skin fibroblasts or peripheral blood lymphocytes from individuals with hereditary cancer or with a genetic disorder predisposing to cancer show an abnormally high frequency of chromatid damage after X-irradiation in G2 phase. The reproducibility of this response suggested that it could provide the basis of an assay for genetic predisposition to cancer. The present blind study tested whether lymphoblastoid cell lines could also be used in this assay. Lymphoblastoid cell lines from patients with Gardner's syndrome (GS) were compared with those from clinically normal controls. In metaphase cells collected during the first 30 min after X-irradiation (58R), frequencies of chromatid breaks and gaps were similar in GS and normal cells. However, in metaphase cells collected from 0.5 to 1.5 h and 1.5 to 2.5 h after X-irradiation, the total unrepaired damage for each GS cell line was greater than that observed in any of the lines from clinically normal controls. The persistence of chromatid damage in the GS cells after X-irradiation suggests a deficiency or imbalance in the repair or processing of the radiation-induced DNA damage. The results show that lymphoblastoid cell lines in early passage can be used in this cytogenetic assay to identify members in a GS family who have the GS gene(s) or other individuals with a genetic predisposition to cancer.

Cells, Cultured↗
PubMed1990

Carrier detection in xeroderma pigmentosum.

We were able to detect clinically normal carriers of xeroderma pigmentosum (XP) genes with coded samples of either peripheral blood lymphocytes or skin fibroblasts, using a cytogenetic assay shown previously to detect individuals with cancer-prone genetic disorders. Metaphase cells of phytohemagglutinin-stimulated T-lymphocytes from eight individuals who are obligate heterozygotes for XP were compared with those from nine normal controls at 1.3, 2.3, and 3.3 h after x-irradiation (58 R) during the G2 phase of the cell cycle. Lymphocytes from the XP heterozygotes had twofold higher frequencies of chromatid breaks or chromatid gaps than normal (P less than 10(-5)) when fixed at 2.3 or 3.3 h after irradiation. Lymphocytes from six XP homozygotes had frequencies of breaks and gaps threefold higher than normal. Skin fibroblasts from an additional obligate XP heterozygote, when fixed approximately 2 h after x-irradiation (68 R), had a twofold higher frequency of chromatid breaks and a fourfold higher frequency of gaps than fibroblasts from a normal control. This frequency of aberrations in cells from the XP heterozygote was approximately half that observed in the XP homozygote. The elevated frequencies of chromatid breaks and gaps after G2 phase x-irradiation may provide the basis of a test for identifying carriers of the XP gene(s) within known XP families.

Adolescent↗
PubMed1990

A modified Bonferroni method for discrete data.

The Bonferroni adjustment for multiple comparisons is a simple and useful method of controlling the overall false positive error rate when several significance tests are performed in the evaluation of an experiment. In situations with categorical data, the test statistics have discrete distributions. The discreteness of the null distributions can be exploited to reduce the number of significance tests taken into account in the Bonferroni procedure. This reduction is accomplished by using only the information contained in the marginal totals.

Animals↗
PubMed1990

Chromosome aberrations in relation to radiation dose following partial-body exposures in three populations.

Structural chromosome aberrations were evaluated in peripheral blood samples obtained from three populations exposed to partial-body irradiation. These included 143 persons who received radiotherapy for enlarged thymus glands during infancy and 50 sibling controls; 79 persons irradiated for enlarged tonsils and 81 persons surgically treated for the same condition during childhood; and 77 women frequently exposed as young adults to fluoroscopic chest X rays during lung collapse treatment for tuberculosis (TB) and 66 women of similar ages treated for TB with other therapies. Radiation exposures occurred 30 and more years before blood was drawn. Doses to active bone marrow averaged over the entire body were 21, 6, and 14 cGy for the exposed thymic, tonsil, and TB subjects, respectively. Two hundred metaphases were scored for each subject, and the frequencies of symmetrical (stable) and asymmetrical (unstable) chromosome aberrations were quantified in 97,200 metaphases. Cells with stable aberrations were detected with greater frequency in the irradiated subjects compared with nonirradiated subjects in all three populations, and an overall test for an association between stable aberrations and partial-body ionizing radiation was highly significant (P less than 0.001). We found no evidence that radiation-induced aberrations varied by age at exposure. These data show that exposure of children or young adults to partial-body fractionated radiation can result in detectable increased frequencies of stable chromosome aberrations in circulating lymphocytes 30 years later, and that these aberrations appear to be informative as biological markers of population exposure.

Chromosome Aberrations↗