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Biomedical subjects

L C Backer

Publications and source records attributed to L C Backer.

At least 19 recordsLinked to original sources
PubMed2001

Pet dogs as sentinels for environmental contamination.

The presence of environmental contaminants in air, water and food may pose significant health risks to the exposed human population. However, problems associated with assessing chronic exposure to low doses of environmental chemicals, multiple exposure routes, diseases with long latency periods, and non-specific health outcomes make it difficult to conduct the appropriate human epidemiologic studies. It may be useful to complement human epidemiology with animal studies. Animals monitored or evaluated in situ for the appropriate suite of endpoints can provide information about both exposure levels and potential adverse health effects. Animals have served as sentinel indicators for health effects associated with a number of environmental exposures, including pesticides and asbestos. Pet dogs may be particularly valuable sentinels because they share the human environment. In addition, dogs respond to many toxic insults in ways analogous to humans, they have physiologically compressed life spans, and they are free from some important lifestyle risk factors for disease. An example of how pet dogs may be used as sentinels for potential human health hazards involves a study of the genotoxic effects resulting from exposure to a mixture of chemicals from nearby Superfund sites. We conducted a cross-sectional study of exposed dogs (living in the community with the Superfund sites) and controls (living in a nearby community). The pet owners completed a questionnaire, and we collected a blood sample from each dog. The blood samples were analyzed for standard clinical parameters and assays for possible genotoxic effects (peripheral blood lymphocyte micronucleus frequency and lymphocyte subtyping). Pet dogs living near the Superfund sites had a higher micronucleus frequency than control animals, suggesting that the dogs may have been exposed to environmental contaminants from these sites.

Alanine Transaminase↗
PubMed2001

Environmental public health surveillance: possible estuary-associated syndrome.

Public health surveillance involves the collection, analysis, and dissemination of data for use in public health practice. A surveillance system includes the capacity to collect and analyze data as well as the ability to disseminate the data to public health agencies that can undertake effective prevention and control activities. An emerging issue in environmental public health surveillance involves human exposure to the toxins produced by microorganisms present in oceans and estuaries. One of these organisms is Pfiesteria piscicida Steidinger & Burkholder, a dinoflagellate found in estuaries along the Atlantic and gulf coasts of the United States. There have been reports of both human illness associated with occupational exposures to concentrated laboratory cultures of P. piscicida and massive fill kills associated with the presence of the organism in rivers and estuaries. These reports, and anecdotal reports from people who worked on rivers where the organism has been found, generated concern that environmental exposures to P. piscicida, similar organisms, or perhaps a toxin or toxins produced by the organism(s), could cause adverse human health effects. To begin to evaluate the public health burden associated with P. piscicida, investigators from the National Center for Environmental Health at Centers for Disease Control and Prevention and health agencies from states along the Atlantic coast collaborated to develop a passive surveillance system for collecting, classifying, and tracking public inquiries about the organism. Specifically, the group developed exposure and symptom criteria and developed data collection and reporting capabilities to capture the human health parameters collectively referred to as possible estuary-associated syndrome (PEAS). The surveillance system was implemented in six states (Delaware, Florida, Maryland, North Carolina, South Carolina, Virginia) beginning in June 1998. From 1 June 1998 through 30 June 2001, the six state health agencies participating in the PEAS surveillance system received 3,859 calls: 3,768 callers requested information and 91 callers reported symptoms. Five individuals have been identified as meeting PEAS criteria.

Animals↗
PubMed2000

Assessing the acute gastrointestinal effects of ingesting naturally occurring, high levels of sulfate in drinking water.

Concerns regarding the health effects from sulfate in drinking water have been raised because of reports that diarrhea may be associated with ingesting water that contains high levels of sulfate. Of particular concern are groups in the general population (i.e., infants and transients) that may be at greater risk from the laxative effects of sulfate when they switch abruptly to drinking water with high sulfate concentrations. There have been a number of studies of the effects of sulfate in the drinking water of domestic animals (cattle, swine, and poultry), and most report minimal adverse effects from exposure to fairly high levels of sulfate. Anecdotal reports and case studies suggest that people suffer gastrointestinal effects when exposed to drinking water containing high levels of sulfate. However, there have been few experimental studies of the effects of sulfate on adults, and only two epidemiologic studies designed to assess the effects of high levels of sulfate on infants, and it is not yet possible to accurately determine the concentration of sulfate in drinking water that will produce adverse human health effects.

Animals↗
PubMed1999

Animals as sentinels of human health hazards of environmental chemicals.

A workshop titled "Using Sentinel Species Data to Address the Potential Human Health Effects of Chemicals in the Environment," sponsored by the U.S. Army Center for Environmental Health Research, the National Center for Environmental Assessment of the EPA, and the Agency for Toxic Substances and Disease Registry, was held to consider the use of sentinel and surrogate animal species data for evaluating the potential human health effects of chemicals in the environment. The workshop took a broad view of the sentinel species concept, and included mammalian and nonmammalian species, companion animals, food animals, fish, amphibians, and other wildlife. Sentinel species data included observations of wild animals in field situations as well as experimental animal data. Workshop participants identified potential applications for sentinel species data derived from monitoring programs or serendipitous observations and explored the potential use of such information in human health hazard and risk assessments and for evaluating causes or mechanisms of effect. Although it is unlikely that sentinel species data will be used as the sole determinative factor in evaluating human health concerns, such data can be useful as for additional weight of evidence in a risk assessment, for providing early warning of situations requiring further study, or for monitoring the course of remedial activities. Attention was given to the factors impeding the application of sentinel species approaches and their acceptance in the scientific and regulatory communities. Workshop participants identified a number of critical research needs and opportunities for interagency collaboration that could help advance the use of sentinel species approaches.

Animals↗
PubMed1999

Serum follicle-stimulating hormone and luteinizing hormone levels in women aged 35-60 in the U.S. population: the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994).

OBJECTIVE: The objective of this study was to examine age-specific population-based values for serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in women in the U.S. population. DESIGN: Data were collected from a nationally representative cross-sectional health examination survey that included measurements of follicle-stimulating hormone and luteinizing hormone and information from a personal interview. A total of 3388 women aged 35 to 60 years were examined during the third National Health and Nutrition Examination Survey, 1988-1994. RESULTS: Among U.S. women aged 35-60 years, median FSH and LH levels began to increase for women in their late 40s and reached a plateau for women in their early 50s. This study supports the previously reported association between serum FSH and age (i.e., serum FSH and LH levels increase with age) and smoking (i.e., current smoking was associated with an increased level of serum FSH). At FSH levels of > or = 15 IU/L or > or = 20 IU/L. 70 and 73% of women, respectively, were postmenopausal. Our study also found an interaction between age and oophorectomy. In addition, the present data suggest that women with only one ovary may have higher FSH levels than women with both of their ovaries. CONCLUSIONS: NHANES III provides population-based data that support previously reported associations between serum FSH level and age, smoking, and menopausal status.

Adult↗
PubMed1997

Exposure to regular gasoline and ethanol oxyfuel during refueling in Alaska.

Although most people are thought to receive their highest acute exposures to gasoline while refueling, relatively little is actually known about personal, nonoccupational exposures to gasoline during refueling activities. This study was designed to measure exposures associated with the use of an oxygenated fuel under cold conditions in Fairbanks, Alaska. We compared concentrations of gasoline components in the blood and in the personal breathing zone (PBZ) of people who pumped regular unleaded gasoline (referred to as regular gasoline) with concentrations in the blood of those who pumped an oxygenated fuel that was 10% ethanol (E-10). A subset of participants in a wintertime engine performance study provided blood samples before and after pumping gasoline (30 using regular gasoline and 30 using E-10). The biological and environmental samples were analyzed for selected aromatic volatile organic compounds (VOCs) found in gasoline (benzene, ethylbenzene, toluene, m-/p-xylene, and o-xylene); the biological samples were also analyzed for three chemicals not found in gasoline (1,4-dichlorobenzene, chloroform, and styrene). People in our study had significantly higher levels of gasoline components in their blood after pumping gasoline than they had before pumping gasoline. The changes in VOC levels in blood were similar whether the individuals pumped regular gasoline or the E-10 blend. The analysis of PBZ samples indicated that there were also measurable levels of gasoline components in the air during refueling. The VOC levels in PBZ air were similar for the two groups. In this study, we demonstrate that people are briefly exposed to low (ppm and sub-ppm) levels of known carcinogens and other potentially toxic compounds while pumping gasoline, regardless of the type of gasoline used.

Adult↗
PubMed1991

Evidence that methanol inhalation does not induce chromosome damage in mice.

Mice were exposed by inhalation to 800 or 4000 ppm methanol for 5 days, and cytogenetic effects were analyzed in blood erythrocytes, lung cells, and testicular germ cells. The results were uniformly negative; no increased frequencies of micronuclei in blood cells, of sister-chromatid exchanges, chromosome aberrations, or micronuclei in lung cells, or of synaptonemal complex damage in spermatocytes were found. From the standpoint of risk assessment, these experimental studies do not reveal any evidence of a cytogenetic hazard associated with inhalation of methanol.

Administration, Inhalation↗
PubMed1991

Stage-specific damage to synaptonemal complexes and metaphase chromosomes induced by X rays in male mouse germ cells.

Synaptonemal complexes reveal mutagen-induced effects in germ cell meiotic chromosomes. This study was aimed at characterizing relationships between damage to synaptonemal complexes and metaphase I chromosomes following radiation exposure at various stages of spermatogenesis. Male mice were irradiated with doses of 0, 2, or 4 Gy, and spermatocytes were harvested at times consistent with earlier exposures as spermatogonial stem cells, preleptotene cells (premeiotic DNA synthesis), or meiotic prophase cells. After stem-cell exposure, twice as many rearrangements were observed in synaptonemal complexes as in metaphase I chromosomes. Irradiation during premeiotic DNA synthesis resulted in dose-related increases in synaptonemal complex breakage and rearrangements (including novel forms) and in metaphase chromosomal aberrations. Following prophase exposure, various types and levels of damage to synaptonemal complexes and metaphase chromosomes were observed. Irradiation of zygotene cells led to high frequencies of chromosome multivalents in metaphase I without a correspondingly high level of damage in preceding prophase synaptonemal complexes. Thus irradiation of premeiotic and meiotic cells results in variable relationships between damage to synaptonemal complexes and metaphase chromosomes. Interpretations of these relationships are based upon what is known about both radiation clastogenesis and the structural/temporal relationships between synaptonemal complexes at prophase and chromosomes at metaphase I of meiosis.

Animals↗
PubMed1990

Genotoxicity of inhibitors of DNA topoisomerases I (camptothecin) and II (m-AMSA) in vivo and in vitro.

The present study was designed to determine and compare the clastogenicity of m-AMSA and camptothecin (CAMP) in vivo in mouse bone marrow and peripheral blood lymphocytes (PBLs), and in vitro in mouse lymphoma L5178Y cells. m-AMSA interferes with topoisomerase II to induce double-strand DNA breaks. CAMP interferes with topoisomerase I to induce single-strand DNA breaks. Thus, we expected the two drugs to induce different types of chromosomal aberrations (CAs). However, both drugs produced quantitatively and qualitatively similar numbers and types of aberrations under similar experimental conditions. In mouse bone marrow exposed over and 18-h period, both drugs (3 mg/kg) induced approximately 30 damaged cells, with an average of 0.4 chromatid breaks per cell (in 100 cells analyzed/mouse). In addition, both drugs induced only chromatid-type aberrations in mouse bone marrow in vivo when exposure occurred during G2. Cell cycle specificity was indicated by the absence of CAs when exposure to the drugs occurred in vivo in mouse PBLs during G0. In L5178Y cells, m-AMSA was considerably more potent for the induction of mutations and somewhat more potent for the induction of CAs than CAMP was. In contrast to the in vivo bone marrow results, the drugs induced high levels of both chromatid- and chromosome-type aberrations in vitro. The ultimate types of chromosomal damage induced by m-AMSA and CAMP result from a complex interaction of (i) cell cycle specific variations in topoisomerase enzyme levels, (ii) the abilities of these drugs to interfere with the orderly DNA breakage/reunion associated with topoisomerase activity, and (iii) the processing of the damage resulting from these interactions.

Amsacrine↗
PubMed1990

Bleomycin effects on mouse meiotic chromosomes.

The effects of a radiomimetic chemical, bleomycin (BLM), on meiotic chromosomes was evaluated in mice treated by intraperitoneal (i.p.) or intratesticular (i.t.) injection. Chromosome aberrations were analyzed at meiotic metaphase I, and damage to the synaptonemal complex (SC) was analyzed in meiotic prophase cells. In the metaphase aberration studies, an i.p. injection of 80 mg/kg BLM, timed to precede or coincide with pre-meiotic S phase, led to a significant increase in structural damage (P less than 0.01) in cells reaching metaphase I 12 days after treatment. However, no increases in clastogenic effects were observed at metaphase I after treatment of cells during various stages of prophase. SC analyses in pachytene cells following an i.p. or i.t. injection at S phase revealed various forms of synaptic errors and structural anomalies, including qualitative changes similar to those observed following irradiation. I.p. doses ranging from 25 to 100 mg/kg, and i.t. doses as low as 0.5 mg/kg, caused roughly 6-fold increases over control levels in the number of damaged cells. SC analyses in pachytene cells following BLM treatments 2 days earlier (at leptotene-zygotene) or 16 h earlier (at early-mid pachytene), also revealed induced structural and synaptic anomalies. Following the treatment at early-mid pachytene, there was some suggestion of interference with chiasma formation as evidenced by univalent-like configurations detected at diakinesis-metaphase. It was concluded that BLM is clastogenic for meiotic chromosomes; however, it does not reveal the strong S-independent clastogenic activity at meiosis that is characteristic of its activity at meiosis. SC analysis indicated that some damage is induced at meiotic prophase, although structurally aberrant cells are not recoverable at meiotic metaphase I. The results call forth various possible explanations for germ-line specific responses to BLM clastogenic activity.

Animals↗
PubMed1989

The effects of acrylamide on mouse germ-line and somatic cell chromosomes.

The industrial chemical acrylamide is suspected to induce potentially heritable genetic damage. While several studies in rodents have indicated that this substance can damage spermiogenic cells, resulting in dominant lethals and heritable translocations, cytogenetic assessments of premeiotic and meiotic cells after exposure have produced equivocal results. In the present study, various cytogenetic endpoints in both somatic and germ-line cells from acrylamide-treated mice were evaluated. Sister chromatid exchanges and micronuclei, but not chromosome aberrations, were induced in spleen cells; synaptonemal complex irregularities (asynapsis), but not chromosome aberrations, were induced in germ cells.

Acrylamide↗
PubMed1988

Synaptonemal complex damage as a measure of genotoxicity at meiosis.

Synaptonemal complex aberrations can provide a sensitive measure of chemical-specific alterations to meiotic chromosomes. Mitomycin C, cyclophosphamide, amsacrine, ellipticine, colchicine, vinblastine sulfate, and cis-platin exposures in mice have been shown to cause various patterns of synaptonemal complex structural damage and synaptic irregularity. These effects are suggestive of abnormal homologue pairing/synapsis/recombination effects which, theoretically, could be implicated in mechanisms leading to aneuploidy and other potentially heritable chromosomal disorders.

Alkaloids↗
PubMed1988

Synaptonemal complex damage induced by clastogenic and anti-mitotic chemicals: implications for non-disjunction and aneuploidy.

Mice were treated with mitomycin C, cyclophosphamide, amsacrine, colchicine, or vinblastine sulfate, and meiotic prophase cells analyzed for synaptonemal complex (SC) damage. All test agents caused synaptonemal complex breakage and synapsis irregularities, although propensities for inducing specific types of damage at S-phase or prophase stages varied among the chemicals. The data indicate that SC analysis can reveal chemical-specific alterations to meiotic homologue pairing/synapsis which have not generally been recognized, and which theoretically may be implicated in non-disjunction.

Aneuploidy↗
PubMed1988

Synaptonemal complex damage in relation to meiotic chromosome aberrations after exposure of male mice to cyclophosphamide.

The genetic implications of induced synaptonemal complex (SC) damage are not known. However, on theoretical grounds, such aberrations could be involved in mechanisms leading to potentially heritable defects. Cyclophosphamide (CP), a chemical reported to cause structural and numerical chromosomal aberrations in the mouse, was used to determine if SC damage observed in meiotic prophase is related to subsequent metaphase chromosomal aberrations. Male mice were injected i.p. with CP. In some instances, mice were also injected simultaneously with tritiated thymidine to label DNA so that cells could be tracked autoradiographically through spermatogenesis. Prophase, primary metaphase (M1), and secondary metaphase (M2) samples were sequentially harvested at appropriate times from the same individual, and nuclei were examined for aberrations. Correlation coefficients between SC and metaphase chromosome aberrations were calculated. The inclusion of tritium labeling increased the number and significance of positive correlations. Positive correlations were found between (1) dose-dependent total SC damage and damage to M1, and to a lesser extent, M2 chromosomes; (2) SC breaks/fragments and M1 chains/rings as well as isochromatid breaks/fragments; (3) SC asynapsis and M1 chromatid breaks/fragments; (4) SC multi-axial configurations and M1 chains/rings as well as isochromatid and chromatid breaks/fragments; and (5) SC multi-axial configurations and M2 hyperploidy. These correlations do not define mechanistic or causal relationships between SC and chromosomal damage. However, taken together with the observation that induced SC damage is many times greater than ensuing metaphase chromosome damage, they substantiate SC analysis as a highly sensitive indicator of potentially heritable effects of this (and presumably other) genotoxic agents.

Aneuploidy↗
PubMed1986

Sister chromatid exchange and chromosome aberration analyses in mice after in vivo exposure to acrylonitrile, styrene, or butadiene monoxide.

The use of polymers in plastic and rubber products has generated concern that monomers potentially active in biological systems may be eluted from these substances. We have evaluated two such monomers, acrylonitrile and styrene, for the induction of chromosome damage in mice. Butadiene monoxide, a presumed metabolite of a third important monomer, 1,3-butadiene, was also tested. These chemicals were administered as a single intraperitoneal injection; sister chromatid exchanges and chromosome aberrations were analyzed in bone marrow cells. Acrylonitrile and styrene were largely negative for these endpoints when tested at doses ranging to 60 mg/kg and 1,000 mg/kg, respectively. Butadiene monoxide, which previously has not been tested in a mammalian system, was determined to be a very effective inducer of sister chromatid exchanges and chromosome aberrations. Both endpoints showed a clear dose response and a greater than ten-fold increase over control levels at high doses. These studies represent an initial step in our efforts to evaluate genetic risk associated with exposure to common polymeric chemicals.

Acrylonitrile↗
PubMed1986

Tumorigenesis and genotoxicity of ethyl carbamate and vinyl carbamate in rodent cells.

Vinyl carbamate (VC) is a suspect metabolic intermediate in ethyl carbamate (EC) carcinogenesis. In the present studies, EC and VC were evaluated for their relative abilities to induce adenomas and sister chromatid exchanges (SCEs) in lung cells of A/J, C3HeB/FeJ, and C57BL/6J strain mice. For both end points, animals were administered a single i.p. injection of the test chemical. Percentage of mice with adenomas and number of adenomas per mouse were compared among the three strains 24 weeks following exposure to EC or VC. Although the relative order of strain sensitivity was the same for both chemicals: A/J greater than C57BL/6J greater than C3HeB/FeJ, VC was much more potent than EC. For SCE analysis of primary lung cells cultured from treated animals, EC and VC showed potency differences similar to those observed for tumorigenesis. All three mouse strains revealed significant dose-dependent increases in SCE frequency. However, there was no strain specificity for this effect. SCE persistence over time was also compared in treated A/J and C57BL/6J mice. Although EC- and VC-induced SCE frequencies declined over a 2-week observation period, again, there was no strain specificity for this effect. VC was also tested for enhancement of SA7 virus transformation of Syrian hamster embryo cells. Significant concentration-dependent increases in cell transformation frequency were observed.

Animals↗