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Biomedical subjects

R S Yang

Publications and source records attributed to R S Yang.

At least 91 records · Page 5Linked to original sources
PubMed1995

Surgical indications for Ewing's sarcoma of the pelvis.

BACKGROUND: Despite advances in adjuvant therapy, Ewing's sarcoma of the pelvis remains an anatomic site with a poor prognosis. This study evaluate the role of surgery in the management of patients with pelvic Ewing's sarcoma who also received conventional radiation therapy and chemotherapy. METHODS: From May 1978 to February 1994, 19 patients with Stage IIB Ewing's sarcoma of the pelvis were treated at the UCLA Medical Center (Los Angeles, CA). There were eight lesions of the ilium, two of the sacrum, and nine involving two adjoining regions of pelvis. All patients received conventional medical management. The 19 patients were divided into two groups according to treatment modality. A group of 12 patients (Group A) had surgical resection, and their results were compared with those of another group of 7 patients (Group B) who did not have surgery. RESULTS: The 5-year cumulative survival (Kaplan-Meier method) was 39% for all patients, 51% for Group A, and 18% for Group B. The 3-year cumulative survival was 59% for all patients, 72% for Group A, and 36% for Group B. Although the survival rate of Group A seemed better than that of Group B, the difference was not statistically significant (P = 0.093, log rank method). This study also suggested that, regardless of treatment modality, the outcome of patients with lesions involving two adjoining pelvic bones was poorer than that of those with a single lesion. In Group A, the 3-year cumulative survival rate for patients with single bone lesions (n = 8) was 86% and for patients with lesions involving two adjoining pelvic bones (n = 4) was 50% (P = 0.045, log rank method). Furthermore, the statistical analysis of the combined data of the single pelvic bone lesions in UCLA and that of Mayo Clinic series (n = 16 for surgery group and n = 15 for nonsurgery group) confirmed the better results for the surgical patients, which was consistent with the results from the Mayo Clinic with an even greater significance (P < 0.002). CONCLUSION: This study demonstrates that surgery plus chemotherapy and radiation therapy is helpful for treating patients with pelvic Ewing's sarcoma so long as the tumor is limited to a single pelvic bone.

Adolescent↗
PubMed1995

High grade soft tissue sarcoma of the flexor fossae. Size rather than compartmental status determine prognosis.

BACKGROUND: High grade soft tissue sarcoma arising in the popliteal space, axilla, and antecubital fossae (flexor fossae tumors) have by convention been classified as extracompartmental tumors by the accepted staging and grading criteria of the Musculoskeletal Tumor Society (MSTS). Advances in neoadjuvant chemotherapy and radiation therapy have made surgical resection more feasible. The hypothesis to be tested is that compartmental status may not be of prognostic significance if the tumor is adjusted for size, histologic grade, and distant metastasis after undergoing adjuvant chemotherapy and radiation. METHODS: From June 1976 to December 1992, 22 patients with high grade soft tissue sarcomas of the flexor fossae (Group A) were treated at UCLA Medical Center. The histologic subtypes were liposarcoma (five), synovial cell sarcoma (eight), malignant fibrous histiocytoma (four), leiomyosarcoma (two), angiosarcoma (two), and rhabdomyosarcoma (one). The popliteal fossa was the location in 11, the axilla in 10, and the antecubital fossa in 1. Wide resection was attempted in all patients after preoperative chemotherapy and radiation therapy. Amputation was performed in 5 patients because of repeated or extensive recurrent tumor. A group of 77 patients (Group B) with high grade soft tissue sarcoma located within an extremity compartment were chosen to test the hypothesis that survival of patients with tumors in the flexor fossae is equal to that of patients with intracompartmental tumors of similar size and grade if both are given adjuvant therapy. This group was chosen so that histologic subtype, size, sex, and location would be similar in the two groups. The authors selected thigh and calf tumors for comparison with popliteal fossa tumors and periscapular, deltoid, and arm tumors for comparison with axilla and antecubital fossae tumors. All of these patients had similar treatment and follow-up protocols. The median follow-up of survivors in Group A was 104 months and for patients in Group B was 79 months. RESULTS: The 5-year cumulative survival rate (Kaplan-Meier method) of patients in Group A was 76%, and 67% for those in Group B. The difference was not significant. Three patients in Group A (14%) and 17 (22%) in Group B had local tumor recurrence. Eight patients in Group A (36%) and 27 (35%) in Group B had lung metastases. Age, sex, histologic subtype, and surgical margins did not affect survival outcomes, lung metastasis, and local recurrence. However, patients with larger tumors (maximum dimension > or = 8 cm or cross-sectional area > or = 40 cm2) had significantly poorer survival, more metastases, and local recurrences. CONCLUSION: Flexor fossae sarcomas do not have a poorer prognosis than extremity intracompartmental tumors when adjusted for size, distant metastasis, and histologic grade when they are treated with adjuvant radiation therapy, chemotherapy, and surgery.

Adolescent↗
PubMed1995

Assessment of the reproductive toxicity of a complex mixture of 25 groundwater contaminants in mice and rats.

The potential reproductive toxicity of a mixture of 25 chemicals (MIX) formulated to simulate contaminated groundwater supplies near hazardous waste dumps was evaluated in CD-1 Swiss mice and Sprague-Dawley rats using the reproductive assessment by continuous breeding protocol. Male and female mice and rats were exposed to MIX in the drinking water at concentrations of 1, 5, and 10% of a technically achievable stock solution. For mice, body weight and feed consumption were not affected by MIX but water consumption was decreased for both the 5 and 10% MIX groups in both F0 and F1 animals. For F0 mice, the number of live pups/litter was decreased at 10% MIX and the number of females/litter was decreased 10 and 17% at the mid and high MIX dose, respectively. Vaginal cytology was normal, as were testis weight and testicular spermatid head count. For F1 mice, fertility was unaffected, but there was a decreased number of female pups/litter (19%) and a decreased adjusted live pup weight at 10% MIX. At necropsy, cauda epididymal sperm concentration and spermatid head count were reduced (20%) in the presence of normal testis, epididymis, prostate, seminal vesicle, liver, and kidney/adrenal weight. Female estrous cyclicity was altered at 5 and 10% MIX with normal kidney/adrenal, uterus, and ovary/oviduct weight. For rats, F0 body weight and feed consumption were not affected by MIX but water consumption was decreased 10, 30, and 40% in the low-, medium-, and high-dose MIX groups, respectively, and 39% in the high-dose MIX F1 animals. Rat fertility was normal but there was a decreased number of male pups/litter (11%) and a decreased live pup weight (6%) at 10% MIX. Male and female (F1) pup weights were decreased on Postnatal Days 0, 4, 7, 14, and 21 (10% MIX) and remained lower through necropsy on Day 120 +/- 10. F1 fertility was normal but F2 pup weights were decreased (10% MIX). At necropsy, F1 (10% MIX) male body weight was decreased 16% and relative kidney, testis, epididymis, and prostate weights were increased in the presence of normal sperm concentration percentage motile sperm and percentage abnormal sperm. Estrous cyclicity was normal as were kidney/adrenal and ovary weight while female liver weight was reduced 14%. In summary, a "cocktail" of 25 chemicals commonly found in contaminated groundwater at or near hazardous waste sites was administered in drinking water at doses which resulted in severely decreased water consumption in both mice and rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Toxicology of methyl bromide.

Methyl bromide is widely used as an insecticidal fumigant in food supplies, warehouses, barges, buildings, and furniture. Its popularity as a fumigant is largely attributable to its high toxicity to many pests, the variety of settings in which it can be applied, its ability to penetrate the fumigated substances, and its rapid dissipation following application. Because of its frequent use around humans and human-related activities and its high acute toxicity, methyl bromide-related fatal accidents have occurred. The primary route for human exposure to methyl bromide is inhalation. In California, the most frequent cause of death from methyl bromide exposure in recent years has been unauthorized entry into structures under fumigation. The most frequently reported lesions included pulmonary edema, congestion, and hemorrhage. In recent years, a great deal of effort has been given to the characterization of the toxicity of methyl bromide because of its commercial value and its direct and indirect economic importance. Methyl bromide is acutely very toxic. Subchronically and chronically, the principal target site for methyl bromide appears to be the central nervous system. However, there was no evidence for carcinogenic activity of methyl bromide following the normal environmental exposure routes of inhalation or oral intake through residue on foods. Methyl bromide is clearly genotoxic in vitro and in vivo, as evidenced by the positive results from various tests. The mechanism of toxicity for methyl bromide is currently uncertain, although its alkylating property as well as the possibility of forming a reactive intermediate through metabolic transformation remain attractive hypotheses.

Alkylation↗
PubMed1995

Periprosthetic bone mineral density of the distal femur after total knee arthroplasty.

Evaluation of the bone mineral density (BMD) was performed in the distal femur around the femoral component of a total knee prosthesis. A total of 48 females were enrolled for this study, including 14 with osteoarthritis of one knee undergoing total knee arthroplasty (TKA) with an Osteonics prosthesis, 14 with osteoarthritis of one knee undergoing TKA with a Whiteside prosthesis, and 20 age-matched normal controls. The BMDs of both knees were measured before operation, and then at 3, 6 and 12 months after operation. The preliminary results demonstrate a significant progressive decrease of BMD in the distal femur of the operated knees after TKA, whereas the BMD of the non-operated knees remains stable. The ratio of BMD between the operated femur and the non-operated femur began to decrease 6 months after operation, and was most obvious at the end of the first year (ranging from 7% to 27%). Further investigation is essential to determine the clinical significance of this loss of periprosthetic bone.

Absorptiometry, Photon↗
PubMed1995

The application of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling for exploring risk assessment approaches of chemical mixtures.

When dealing with health impacts of environmental or occupational exposure such as groundwater contamination from or remediation effort associated with hazardous waste sites, we are obviously not facing individual, single chemicals. Thus, we are immediately confronted with the following questions: (1) Is single chemical risk assessment approach applicable to the multiple chemicals in hazardous waste sites? (2) How do we handle risk assessment of chemical mixtures? Although there were pioneering and commendable efforts from the USEPA to formulate guidelines for risk assessment of chemical mixtures, these guidelines were principally based on additivity concept. As new scientific advances are made, improvement and refinement of risk assessment methodology will be anticipated. At Colorado State University (CSU), our research effort is devoted to the challenges and potential applications of physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling in the risk assessment of chemical mixtures. With the ultimate goal of Predictive Toxicology, 3 specific research projects are described: (1) PBPK/PD modeling of toxicologic interactions between trichloroethylene (TCE) and 1,1-dichloroethylene (1,1-DCE) and the investigation and defining of an 'Interaction Threshold'; (2) PBPK/PD modeling of toxicologic interactions between Kepone and carbon tetrachloride (CCl4) and the coupling of Monte Carlo simulation for the prediction of acute toxicity; (3) PBPK modeling of the inhibition of pharmacokinetics and enzyme kinetics of TCE caused by low-level, repeated dosing of a chemical mixture of 7 groundwater contaminants. Since this paper is meant to be a commentary and the emphasis is on approaches for dealing with chemical mixtures, detailed presentation of data is avoided. These examples illustrate partially our ongoing research activities and the related ideas with respect to possible novel risk assessment applications to chemical mixtures.

Animals↗
PubMed1995

The use of physiologically-based pharmacokinetic/pharmacodynamic dosimetry models for chemical mixtures.

Human exposure to chemicals is rarely, if ever, limited to a single chemical. Therefore, it is essential that we consider multiple chemical effects and interactions in our risk assessment process. However, with the almost infinitely large number of chemical mixtures in the environment, systematic studies of the toxicology of these chemical mixtures with conventional methodologies and approaches are impossible because of the immense resources and unrealistically long durations required. Thus, the development of 'Predictive and Alternative Toxicology' is imperative. At Colorado State University (CSU), our research effort is entirely devoted to this challenge. In order to have a reasonable chance to deal with the complex issue of toxicology of chemical mixtures, we believe that the following concepts must be considered: (1) the utilization of computer, (2) the exploitation of mathematical/statistical methodologies; (3) developing very focused, mechanistically based, and short-term toxicology studies; (4) coupling computer/mathematical modeling with mechanistically-based toxicology. Our strategy therefore the utilization of physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling, coupled with very focused, model-directed toxicology experiments as well as other statistical/mathematical methodologies such as Monte Carlo simulation, isobolographic analysis, and response surface methodology. We believe that 'Predictive and Alternative Toxicology' in terms of tissue dosimetry at the pharmacokinetic and pharmacodynamic levels is achievable with simple and complex but chemically defined mixtures. In this presentation, we describe two ongoing research projects as an illustration of our 'Bottom-Up' and 'Top-Down' approaches for handling the chemical mixtures: (1) PBPK/PD modeling of toxicologic interactions between Kepone and carbon tetrachloride (CCl4) and the coupling of Monte Carlo simulation for the prediction of acute toxicity; (2) the conceptual development of PBPK/PD modeling for a more complex chemical mixture of seven groundwater contaminants from hazardous waste sites and the consideration of subfractionation of this chemical mixture.

Animals↗
PubMed1995

The Arg-Gly-Asp-containing peptide, rhodostomin, inhibits in vitro cell adhesion to extracellular matrices and platelet aggregation caused by saos-2 human osteosarcoma cells.

Saos-2 cells, derived from a primary human osteosarcoma, caused dose-dependent platelet aggregation in heparinised human platelet-rich plasma. Saos-2 tumour cell-induced platelet aggregation (TCIPA) was completely inhibited by hirudin but unaffected by apyrase. The cell suspension shortened the plasma recalcification times of normal, factor VIII-deficient and factor IX-deficient human plasmas in a dose-dependent manner. However, the cell suspension did not affect the recalcification time of factor VII-deficient plasma. Moreover, a monoclonal antibody (MAb) against human tissue factor completely abolished TCIPA. Flow cytometric analysis using anti-integrin MAbs as the primary binding ligands demonstrated that the integrin receptors alpha v beta 3, alpha 5 beta 1 and alpha 6 beta 1 were present of Saos-2 cells, which might mediate tumour cell adhesion to extracellular matrix. Rhodostomin, an Arg-Gly-Asp (RGD)-containing snake venom peptide which antagonises the binding of fibrinogen to platelet membrane glycoprotein IIb/IIIa, prevented Saos-2 TCIPA as well as tumour cell adhesion to vitronectin, fibronectin and collagen type I. Likewise, the synthetic peptide Gly-Arg-Gly-Asp-Ser (GRGDS) showed a similar effect. On a molar basis, rhodostomin was about 18,000 and 1000 times, respectively, more potent than GRGDS in inhibiting TCIPA and tumour cell adhesion.

Amino Acid Sequence↗
PubMed1995

A unique pattern of hepatocyte proliferation in F344 rats following long-term exposures to low levels of a chemical mixture of groundwater contaminants.

Most exposures of humans to environmental agents involve mixtures of chemicals, rather than individual chemicals. Some chemicals can cause hepatocellular proliferation and act as neoplastic promoters. Little is known concerning hepatocellular proliferation caused by chemical mixtures such as those found in groundwater at hazardous waste sites. Therefore, a 6 month study was performed to investigate hepatocellular proliferation and histopathological changes in F344 rats after long-term, low-level exposure to a mixture of groundwater contaminants. The seven chemicals used are among the most frequently detected contaminants associated with hazardous waste sites; arsenic, benzene, chloroform, chromium, lead, phenol and trichloroethylene. Male F344 rats were exposed to this mixture, or submixtures of the organic or inorganic chemicals, via drinking water for 6 months. The study design included a time-course experiment (i.e. 3 and 10 days and 1, 3 and 6 months) and a dose-response experiment. Hepatocellular proliferation studies were performed by subcutaneously implanting osmotic mini-pumps to continuously deliver 5-bromo-2'-deoxyuridine for 7 days, which labeled nuclei of proliferating cells. In all groups, there were no differences in weight gain, body weight, liver weight ratios or liver-associated plasma enzymes. Light microscopic evaluation revealed no lesions related to the treatments in any animals. However, significant increases in hepatocellular labeling were observed at the 3 and 10 day and 1 month exposure time points after treatment with the full mixture, as well as the organic or inorganic submixtures. Proliferating hepatocytes expressed a unique labeling pattern surrounding large hepatic veins (0.5-2.0 mm), but not central veins. This did not appear to be a regenerative response due to cytotoxic mechanisms, as assessed by the absence of increased plasma enzyme activity and the absence of hepatocellular lesions.

Animals↗
PubMed1995

Evaluation of the nephrotoxicity of complex mixtures containing organics and metals: advantages and disadvantages of the use of real-world complex mixtures.

As part of a multidisciplinary health effects study, the nephrotoxicity of complex industrial waste mixtures was assessed. Adult, male Fischer 344 rats were gavaged with samples of complex industrial waste and nephrotoxicity evaluated 24 hr later. Of the 10 tested samples, 4 produced increased absolute or relative kidney weight, or both, coupled with a statistically significant alteration in at least one of the measured serum parameters (urea nitrogen (BUN), creatinine (CREAT), and BUN/CREAT ratio). Although the waste samples had been analyzed for a number of organic chemicals and 7 of the 10 samples were analyzed also for 12 elemental metals and metalloids, their nephrotoxicity was not readily predicted from the partial chemical characterization data. Because the chemical form or speciation of the metals was unknown, it was not possible to estimate their contribution to the observed biological response. Various experimental approaches, including use of real-world complex mixtures, chemically defined synthetic mixtures, and simple mixtures, will be necessary to adequately determine the potential human health risk from exposure to complex chemical mixtures.

Animals↗
PubMed1995

Collagen in tendon, ligament, and bone healing. A current review.

Cells that produce a particular type of collagen under normal physiologic circumstances can be induced by certain local triggers to change the amount and type of collagen synthesized. This has become most apparent during bone, tendon, and ligament healing, where cells that once produced the collagen of normal intact tissue are induced to synthesize different types of collagen at the repair site of injured tissue. For example, Type III collagen, not a major component of the extracellular matrix in normal tendons, is believed to be of great advantage during the healing process because of its ability to form rapid crosslinks and precariously stabilize the repair site. Although much is known about the gross histologic changes occurring during tissue healing, little is known about the specific role of the individual collagen types or what influences their development. This review addresses the role of collagen in normal and healing bone, tendon, and ligament. Much experimental effort is needed to uncover the distribution and function of the collagen types within connective tissue elements and the effect of growth factors on the phenotype of collagen produced in these tissue, with the ultimate goal of developing clinical manipulations that take advantage of the unique properties of each type of collagen.

Anterior Cruciate Ligament↗
PubMed1994

The acute metabolic effects of oral tricalcium phosphate and calcium carbonate.

A double-blind study was performed to test the metabolic effects of tricalcium phosphate (TP) and calcium carbonate (CC) on serum calcium (SCa), serum phosphorus (SP), and immunoreactive intact serum parathyroid hormone (SPTH) levels in two groups of 24 subjects. The mean age of young subjects was 29.5 years, and elderly subjects, 65.9 years. These subjects fasted overnight for 12 hours, but with good hydration, before the tests. Following a 2-hour baseline-urine collection, 1200 mg elemental calcium (as CC or TP in tablet form) was chewed and ingested and 2-hour postload urines were collected. Blood was drawn immediately before and at 1, 2, and 4 hours after calcium load. The results showed that SCa and SP increased, whereas SPTH decreased with both preparations. The increment of SCa was similar after oral load of either calcium salt in both groups. The increment of SP after TP load was more than after CC. The urinary calcium/creatinine ratio (UCa/Cr) increased significantly after both preparations in the young group. The urinary phosphorus/creatinine ratio (UP/Cr) did not change significantly following TP, but decreased significantly after CC load in the young subjects. However, in the elderly individuals, the UP/Cr increased after TP load but did not change following CC, with statistical significance. The difference of urinary cyclic adenosine monophosphate/creatinine ratio (UcAMP/Cr) was not significant in both groups with either preparation. In summary, there was a similar rise in SCa and an equivalent fall in SPTH between TP and CC, in both young and elderly individuals.

Administration, Oral↗
PubMed1994

Toxicology studies of a chemical mixture of 25 groundwater contaminants: hepatic and renal assessment, response to carbon tetrachloride challenge, and influence of treatment-induced water restriction.

Because groundwater contamination is an important environmental concern, we examined the hepatic and renal effects of repeated exposure to a mixture of 25 chemicals frequently found in groundwater near hazardous-waste disposal sites and the effect of such exposure on carbon tetrachloride (CCI4) toxicity. Adult male F-344 rats received ad libitum deionized water and feed (Ad Lib Water) or ad libitum 10% MIX (referring to 10% of a technically achievable stock mixture) and feed for 14 d. Because exposure to the 25-chemical mixture via the drinking water resulted in decreased water and feed consumption, restricted deionized water and feed controls (Restricted Water) were included. On d 14, rats were gavaged with 0, 0.0375, 0.05, 0.075 or 0.15 ml CCl4/kg, and hepatic and renal toxicity assessed 24 h later. Little or no hepatic and renal toxicity was observed in rats exposed to 10% MIX alone. No hepatic or renal lesions occurred that could be attributed to 10% MIX alone. Slight but statistically significant alterations, of uncertain biological significance, resulted from the water treatments: 10% MIX increased alanine aminotransferase, urea nitrogen (BUN), and BUN/creatinine ratio; Restricted Water increased 5'-nucleotidase and decreased alkaline phosphatase. Relative kidney weight was increased by both 10% MIX and Restricted Water. CCI4 resulted in significant dosage-dependent hepatotoxicity in all three water treatment groups but had little or no effect on renal indicators of toxicity. Relative to Ad Lib Water, significantly greater hepatotoxicity occurred in both 10% MIX and Restricted Water rats. The response to CCI4 in the Restricted Water rats was similar to that of 10% MIX rats, indicating that a substantial portion of the effect of 10% MIX on CCI4 hepatotoxicity is due to decreased water and feed intake.

Analysis of Variance↗
PubMed1993

Staurosporine-induced morphological changes in the rat osteoblasts.

Treatment of cultured rat osteoblasts with staurosporine caused a rapid outgrowth of long slender cellular processes and the formation of stellate cells. The number of stellate cells increased with higher concentrations of and longer incubation with staurosporine. Scanning electron microscopy (SEM) revealed that the smooth surface of control polygonal cells became ruffled with many long slender cellular processes, thus increasing the cell surface area. Transmission electron microscopy (TEM) of the stellate cells showed a rich accumulation of large lipid droplets in the cytoplasm. Some lipid droplets had coalesced under the cytoplasmic membrane. We suggest that staurosporine has an effect on the differentiation of cultured rat osteoblasts.

Alkaloids↗
PubMed1993

Increased bone growth by local prostaglandin E2 in rats.

The effects of prostaglandin E2 (PGE2) on bone growth were investigated in rats. Daily injection of PGE2 (1, 10, and 100 pmol) was given via local intraosseous route into the metaphysis of the left tibia for 14 days. The contralateral right tibia injected with vehicle and saline was for the control. The rats receiving no injection provided as normal control. The results obtained indicated that PGE2 slightly but significantly decreased the body weight increment without effect on tibial length. The most prominent effect of PGE2 was the increase of metaphyseal bone trabeculae by 45-81% in a dose-dependent manner. The microscopic examination revealed that PGE2 unequivocally increased the new woven bone formation. The bone cell population study showed no difference between the number of osteoblasts and osteoclasts in primary spongiosa of the PGE2-injected limbs and those of contralateral limbs. However, the numbers of osteoblasts and osteoclasts were markedly increased in secondary spongiosa in the PGE2-injected limbs. This finding confirmed a stimulatory role of PGE2 in the bone formation. The local intraosseous injection of PGE2 was proven to be a good model for the study of local growth factors on bone metabolism with a lower effective dose which eliminates the systemic side effects.

Analysis of Variance↗
PubMed1993

Enhancement of myelotoxicity induced by repeated irradiation in mice exposed to a mixture of groundwater contaminants.

As part of a program on the toxicology of chemical mixtures at the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP), hematopoietic functions were studied in female B6C3F1 mice treated with 0, 1%, and 5% of a chemical mixture stock of 25 groundwater contaminants in drinking water for 31.5 weeks. The toxicologic interaction between continuous exposure to groundwater contaminants and stress induced by multiple irradiation on hematopoiesis was investigated. For those mice receiving both the chemical mixture and irradiation, the exposure to the former was continuous throughout the 31.5-week experimental period, whereas whole body irradiations (4 times at 200 rads/each) were carried out at 7-week intervals with the first one at 3.5 weeks. Myelotoxicity assessment was made by determining the number of granulocyte-macrophage progenitor cells (CFU-GM) 1 week after each irradiation and also at 6 weeks following irradiation as a measure of recovery from stress. Non-irradiated mice treated with 5% chemical mixture solution showed suppression of CFU-GM after 15.5 weeks and became progressively more affected (only 70% of controls by 31.5 weeks of treatment). The population of CFU-GM in mice treated with 5% chemical mixture for 4.5 weeks plus irradiation (1 week after first irradiation) was only 22% of the non-irradiated vehicle control group. This combined (i.e., chemical mixture plus irradiation) suppression of CFU-GM intensified after repeated irradiation until the number of CFU-GM was only 10.7% following the fourth irradiation at 25.5 weeks. Thus, irradiation caused a significant reduction in CFU-GMs in all mice but the effects were more pronounced in mice treated with a chemical mixture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Analyses of cytogenetic damage in rodents following exposure to simulated groundwater contaminated with pesticides and a fertilizer.

Male Fischer 344 rats and female B6C3F1 mice were each exposed through their drinking water to a mixture of pesticides and ammonium nitrate that simulated contaminated groundwater in California (California Chemical Mixture [CCM]). Exposures were for 71 or 91 days, respectively. In addition, B6C3F1 female mice were exposed for 91 days to another pesticide and ammonium nitrate mixture (Iowa Chemical Mixture [ICM]) through their drinking water. The spleens were removed from the animals, and the splenocytes were cultured for analyses of sister-chromatid exchange (SCE), chromosome aberrations (CA), and micronuclei (MN) in cytochalasin B-induced binucleate cells. A concentration-related increase in SCEs was found in the splenocytes of the rat at the 1x, 10x and 100x levels of the CCM and at the 100x concentration of the CCM in the mouse. There were no other consistent cytogenetic effects observed with the CCM, and no statistically significant cytogenetic damage was observed in mice exposed to the ICM. Evidence from the literature is discussed in order to infer which chemical or chemicals in the CCM might be responsible for the observed SCE response.

Animals↗