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Biomedical subjects

R L Dixon

Publications and source records attributed to R L Dixon.

At least 19 recordsLinked to original sources
PubMed1979

United States governmental efforts to improve the regulation of toxic substances.

The U.S.'s efforts to improve its regulation of toxic substances presently have their focus in the administration of the Toxic Substance Control Act (TSSC), the Cancer Policy of the regulatory agencies, and the Drug Regulation Reform Act. By improving interagency communication and cooperation as well as establishing a coherent federal approach to the control of toxic substances with public and industrial input, the U.S. government should significantly strengthen the functioning of its regulatory agencies while decreasing the financial burden for everyone involved.

Carcinogens↗
PubMed1979

The inverse compensating filter.

When a single-field technique is used in megavoltage x-ray therapy, a uniform entrance dose is often required. If there is a large variation in source-to-surface distance over the field, an inverse type of compensating filter is necessary to achieve entrance dose uniformity. The production and utilization of these filters is discussed.

Filtration↗
PubMed1979

Assessment of environmental factors affecting male fertility.

Exposure to drinking water containing as much as 500 ppm aluminum chloride for periods of 30, 60, and 90 days had no apparent effect on male reproductive processes. In an attempt to correlate enzyme activity with particular spermatogenic cell types, postnatal development of testicular enzymes was studied. Eight enzymes were selected: hyaluronidase (H), lactate dehydrogenase isoenzyme-X (LDH-X), dehydrogenases of sorbitol (SDH), alpha-glycerophosphate (GPDH), glucose-6-phosphate (G6PDH), malate (MDH), glyceraldehyde-3-phosphate (G3PDH), and isocitrate (ICDH). Enzyme specific activities in testicular homogenates were determined. Two types of enzyme developmental patterns were observed. One was represented by H, LDH-X, SDH, and GPDH; and the other by G6PDH, MDH, G3PDH, and ICDH. The former was characterized by a change in enzyme activities from low in newborn to high in adult while in the latter this pattern was reversed. The two complementary enzyme systems crossed each other at puberty. Prior to puberty, only spermatogonial cells are present; sperm differentiation initiated at puberty adds spermatocytes and spermatids to the testicular cell population. Male rats were exposed to borax in their diet for periods of 30 and 60 days. Concentrations of boron were 0, 500, 1000, and 2000 ppm. At the end of each experimental period, the specific activities of the selected enzymes were determined in the testis and prostate. Correlations of enzyme activity with testicular histology and androgen activities of the male accessory organs were sought. In addition, plasma FSH, LH, and testosterone levels were measured to assess pituitary-testicular interaction. Plasma and testicular boron concentrations were determined and a minimum boron concentration which induced germinal aplasia and male infertility was estimated. In both 30 and 60 day feeding studies, male rats receiving 500 ppm failed to demonstrate any significant adverse effects. In contrast, male rats receiving 100 and 2000 ppm boron displayed a significant loss of germinal elements, although most of the Leydig and Sertoli cells appeared normal. Testicular atrophy was associated with a decrease in seminiferous tubular diameter and a marked reduction of spermatocytes and spermatogenic cells. These morphologic alterations were associated with a concomitant reduction of H, SDH, and LDH-X specific activities. In contrast, the specific activities of G3PDH and MDH were significantly elevated above control. The increase in these enzyme activities can be attributed to the relative enrichment of spermatogonial cells during the loss of spermatocytes and spermiogenic cells. Boron-induced male germinal aplasia was also associated with significantly elevated plasma FSH while plasma LH and testosterone levels were not significantly altered. Plasma testosterone levels were unaltered. Male fertility studies demonstrated that at the 500 ppm boron level, fertility was unaffected. However, at 1000 and 2000 ppm boron, male fertility was significantly reduced. Most effects were reversible within 5 weeks. However, the male group receiving 2000 ppm boron for 60 days remained sterile. There was no dose-related decrease in litter size or fetal death in utero. Therefore, the boron-induced infertility was apparently not due to a dominant lethal effect but rather to germinal aplasia. Boron appears toxic to spermatogenic cells at testicular concentrations of 6-8 ppm.

Administration, Oral↗
PubMed1979

The detoxication of aflatoxin B1 with glutathione in the rat.

1. The deactivation of aflatoxin B1 by glutathione (GSH) has been investigated in rat. Binding of metabolites of aflatoxin B1 to [3H]glutathione in vitro with rat liver microsomes is insignificant. Incubation with rat liver 10 000 g supernatant results in increased binding. Under identical conditions, benzo(a)pyrene metabolites are bound to [3H]glutathione much more than is aflatoxin B1. 2. Pre-treatment of rats with aflatoxin 1 (2 mg/kg) caused depletion in GSH of rat liver with a minimum at 6 h but returning to above normal at 24 h. GSH S-transferase activity was marginally increased at 6 h also and returned to normal at 24 h. 3. Kidney GSH was not significantly decreased, but kidney GSH S-transferase activity showed a sudden increase in 6 h, returning to almost normal at 24 h. 4. Pre-treatment with benzo(a)pyrene (2 mg/kg) caused greater depletion of hepatic GSH than occurred with aflatoxin B1 but did not show any effect on kidney GSH. 5. Hepatic and kidney GSH S-transferase in benzo(a)pyrene-treated rats showed greatest activity at 2 h followed by a gradual fall through 24 h. 6. GSH was therefore a less efficient nucleophile for aflatoxin B1 metabolites than for benzo(a)pyrene metabolites.

Aflatoxins↗
PubMed1978

Carcinogenicity of vinyl chloride and vinylidene chloride.

Exposure of mice to 50, 250, or 1000 ppmm of vinyl chloride (VC) in the air for 6 h/d, 5 d/wk, caused a high incidence of bronchioloalveolar adenoma, mammary gland tumors, and hemangiosarcoma. Mammary gland tumors occurred in the females and included ductular adenocarcinoma and squamous and anaplastic cell carcinomas with metastasis to the lung. Hemangiosarcoma occurred in the liver and, to a lesser extent, in various other organs. The incidence and severity of these tumors increased with the concentration of VC and the length of exposure. Malignant lymphoma involving various organs was observed in several mice. Rats were more resistant to the carcinogenic effects of VC. Exposure of rats to 250 or 1000 ppm of VC caused hemangiosarcoma in the liver. Many rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Extrahepatic hemangiosarcoma also occasionally occurred in other organs. Exposure to 55 ppm of vinylidene chloride (VDC) caused hepatic hemangiosarcoma and probably bronchioloalveolar adenoma in mice. Hemangiosarcoma also occurred in the mesenteric lymph node or subcutaneous tissue in two rats exposed to 55 ppm of VDC.

Aerosols↗
PubMed1978

A film dosimetry system for use in computed tomography.

The authors describe a film dosimetry system for use in calculating the surface dose delivered by a CT scanner. Kodak XV-2 film is wrapped around a cylindrical water-filled phantom and the dose distribution is recorded. This system is easier to use than thermoluminescent dosimetry (TLD) and provides a detailed map of the dose distribution. Comparison with TLD measurements for a variety of CT scanners indicates that an accuracy of +/-15% can be achieved using this system. Dose distributions obtained with several scanners are shown.

Humans↗
PubMed1977

Proton NMR relaxation times in the peripheral blood of cancer patients.

The proton spin lattice relaxation time (T1) of serum and leucocytes of cancer patients and normal volunteers was measured using pulsed NMR techniques. There was no statistically significant difference in the serum T1 values of cancer patients relative to normal. An increase in T1 relative to normal values was detected in the white blood cells of patients with active leukaemia. In these patients T1 fell to normal levels after the initiation of treatment. The variation of leucocyte T1 with the course of the disease for five patients having leukaemia is presented.

Breast Neoplasms↗
PubMed1977

Inhalation toxicity of vinyl chloride and vinylidene chloride.

Exposure of mice to 1000 ppm of vinyl chloride (VC), 6 hr/day, 5 days/week, caused some acute deaths with toxic hepatitis and marked tubular necrosis of the renal cortex. Starting the sixth month, mice exposed to 1000, 250, or 50 ppm of VC became lethargic, lost weight quickly, and died. Only a few mice exposed to 50 ppm survived for 12 months. Pulmonary macrophage count was elevated in some mice. There was a high incidence of bronchiolo-alveolar adenoma, mammary gland tumors including ductular adenocarcinoma, squamous and anaplastic cell carcinomas with metastasis to the lung, and hemangiosarcoma in the liver, and, to a lesser extent, in some other organs. The incidence of these tumors quickly increased, and the severity was in direct proportion to the levels of VC and the length of exposure. Malignant lymphoma involving various organs was observed in a few mice. Rats were more resistant to the toxic effects of VC. Exposure to 1000 ppm slightly depressed the body weight of the females. Exposures of 250 or 1000 ppm caused a number of deaths and hemangiosarcoma in the liver starting the ninth month. Most rats with hepatic hemangiosarcoma also developed hemangiosarcoma in the lung. Hemangiosarcoma occasionally occurred in other tissues of one or two rats exposed to 50 ppm or higher level of VC. Exposure of mice to 55 ppm of vinylidene chloride (VDC) also caused a few acute deaths and a few hepatic hemangiosarcomas. Inflammatory, degenerative, and mitotic changes occurred in the liver. No mouse exposed to VDC developed any mammary gland tumors. Several mice had bronchioloalveolar adenoma. Exposure of rats to 55 ppm of VDC slightly depressed the body weight. Hemangiosarcoma occurred in the mesenteric lymph node or subcutaneous tissue in two rats.

Adenoma↗
PubMed1976

The routine use of graphic data handlers in a radiotherapy department.

Graphic data handlers are helpful in routine dosimetry. The authors describe a computer program using a graphic digitizer which facilitates determination of the equivalent square of an irregularly shaped field. The digitizer can also be used together with an incremental plotter to produce patterns by which Styrofoam molds can be cut for field-defining blocks. Both programs are designed to be used at a remote time-sharing computer station.

Computers↗
PubMed1976

Problems in extrapolating toxicity data for laboratory animals to man.

Some of the problems in extrapolating laboratory animal toxicity data to man are considered. The quantitative predictiveness of preclinical studies of anticancer drugs using dogs and monkeys for man has also been examined. The relationship between the maximum tolerated dose (MTD) in the dog, monkey, and the more sensitive of the two species and clinical observations are discussed. The effectiveness of using doses expressed on the basis of body weight (mg/kg) and body surface area (mg/m2) are compared. A method is introduced to assess the "statistical risk" associated with the extrapolation of the initial clinical (phase I) dose from experimental animal data. The best clinical prediction is obtained when one uses the experimental MTD expressed in mg/kg for the more sensitive of the large animal species (dogs or monkeys). The clinical introduction of a new anticancer agent at a dose 1/10 the MTD in the more sensitive species carries a statistical risk of about 3%; that is, the initial doses of about 3 of every 100 new drugs introduced into the clinic will produce some toxic effects in man. These same data have been extended theoretically to the total population and toxic chemicals in general. Reliable extrapolation from laboratory test models to man requires a much more complete understanding of structure--activity relationships, pharmacokinetic factors, and mechanisms of toxicity.

Animals↗
PubMed1976

Methods to assess reproductive effects of environmental chemicals: studies of cadmium and boron administered orally.

Results of a U.S.S.R.--U.S. cooperative laboratory effort to improve and validate experimental techniques used to assess subtle reproductive effects in male laboratory animals are reported. The present studies attempted to evaluate the reproductive toxicity of cadmium as cadmium chloride and boron as borax (Na2B4O7) and to investigate the mechanism of toxicity in the rat following acute and subchronic oral exposure. In vitro cell separation techniques, in vivo serial mating tests, and plasma assays for hormones were utilized. Effects on the seminal vesicle and prostate were evaluated with chemical and enzyme assays. Clinical chemistry was monitored routinely. Acute oral doses, expressed as boron were 45, 150, and 450 mg/kg while doses for cadmium equivalent were 6.25, 12.5, and 25 mg/kg. Rats were also allowed free access to drinking water containing either boron (0.3, 1.0, and 6.0 mg/l.) or cadmium (0.001, and 0.l mg/l.) for 90 days. Randomly selected animals were studied following 30, 60, and 90 days of treatment. These initial studies, utilizing a variety of methods to assess the reproductive toxicity of environmental substances in male animals, suggest that cadmium and boron at the concentrations and dose regimens tested are without significant reproductive toxicity.

Animals↗
PubMed1976

Modification of renal tumorigenic effect of streptozotocin by nicotinamide: spontaneous reversibility of streptozotocin diabetes.

The renal oncogenic activity of streptozotocin in male Holtzman rats was significantly decreased by nicotinamide. Adenomas of the kidney were noted in 77% (21/28) of the animals treated with single iv dose of the streptozotocin, 50 mg/kg, while only 18% (5/28) of animals given nicotinamide ip, 350 mg/kg, 10 min before and 180 min after the same dose of streptozotocin had demonstrable renal tumors. Moreover, the renal adenomas induced by streptozotocin alone occurred sooner and were generally larger when compared with those in the animals treated with the nicotinamide-streptozotocin combination. The 50 mg/kg dose of streptozotocin was diabetogenic in all rats, but the diabetic state was not permanent. Spontaneous recovery from the diabetes was first noted after 8 and 10 months of followup, and after 16 months none of the surviving rats were diabetic.

Adenocarcinoma↗
PubMed1975

Effects of mercury on spermatogenesis studied by velocity sedimentation cell separation and serial mating.

Recently the potential toxicity of environmental mercury has become a major concern. Human tissues contain mercury due to daily environmental exposure. Nearly all of the mercury contaminating food is in the form of methylmercury complexes, due to the biotransformation of inorganic mercury. This report compares the reproductive effects of methylmercury hydroxide and mercuric chloride in male mice. The mercuric compounds were administered intraperitoneally once at a dose of 1 mg/kg (based on Hg++ concentration), or spermatogenic cells were exposed in vitro to Hg+ concentrations ranging from 10(-3) to 10(-8)M. Spermatogenic cells were separated for biochemical studies using the velocity sedimentation technique, and in vivo serial mating was used to assess fertility. The effects of CH3Hg+ or Hg++ on the uptake of 3H-thymidine by spermatogonia, 3H-uridine by early elongated spermatids, and 3H-L-leucine by late elongated spermatids were studied. These in vitro experiments indicated that at 1-(-3) m CH2HgOH reduced thymidine incorporation by spermatogonia by 40%, uridine incorporation by elongated spermatids by 39% and L-leucine incorporation by late elongated spermatids by 40%. Results obtained with HgCl2 were similar but of lesser magnitude. In vivo administration of CH3HgOH and HgCl2 significantly inhibited the uptake of thymidine, uridine and L-leucine by their respective spermatogenic cells. Fertility profiles obtained from serial mating studies indicated that the primary effect of CH3HgOH was on spermatogonial cells, premeiotic spermatocytes and early elongated spermatids, with no apparent effect on spermatozoa in testis, peididymis or vas deferentia. HgCl2 also primarily affected spermatogonial and premeiotic cells, but the effect was less than that seen with CH3HgOH. Statistical analysis indicated significant antifertility effects. Inhibition of uptake of thymidine and uridine was well correlated with the functionality of these cells as reflected in the fertility profile, excep for L-leucine uptake. Mercury ion-induced antifertility effects at the dosage used in these experiments are reversible. Thus, these results suggest spermatogenic effects of methylmercury complexes which might have important health consequences in man.

Animals↗