PubMed Health⌕ Search

Biomedical subjects

R E Albert

Publications and source records attributed to R E Albert.

At least 91 records · Page 5Linked to original sources

Dose response for benzo(a)pyrene adducts in mouse epidermal DNA.

The dose dependency of the binding of benzo(a)pyrene (BaP) with DNA of mouse epidermis was investigated. BaP-conjugated epidermal DNA was isolated and enzymatically degraded to deoxyribonucleosides. The BaP-DNA adducts were separated by Sephadex LH-20 column or high-performance liquid chromatography. Two major BaP-DNA adducts were found. One was in the region of the elution profile that contained polycyclic aromatic hydrocarbons adducted to deoxyribonucleosides. The other adduct was eluted from Sephadex LH-20 and high-performance liquid chromatography columns before the deoxyribonucleosides and after deoxyribonucleotides. Both adducts of BaP in epidermal DNA reached a maximum 7 hr after a single skin application, and subsequently little, if any, loss of adducts was observed for 49 hr. Both adducts varied as a linear function for topical doses in the range from 0.01 to 300 microgram/mouse. The formation of DNA adducts by BaP occurred in proportion to dose at doses several orders of magnitude below those that are feasible to test for carcinogenicity.

Animals↗

Effects of short-term exposures to sulfuric acid and ammonium sulfate aerosols upon bronchial airway function in the donkey.

The effects of one-hour inhalation exposures to 0.3-0.6 micrometer H2SO4 and (NH4)2SO4 aerosols in the donkey were studied in terms of alterations in pulmonary flow resistance and dynamic compliance, and changes in the regional deposition and tracheobronchial mucocilliary clearance of an inert test aerosol. Short-term slowing of clearance followed certain single exposures to H2SO4 at 194-1364 microgram/m3 in three of four animals, while two of the four demonstrated a more persistent slowing of their clearance. These exposure levels produced no measurable change in resistance, compliance or regional deposition. Exposures to (NH4)SO4 up to approximately 2000 microgram/m3 had no mearurable effect upon resistance, compliance, regional deposition or mucociliary clearance.

Aerosols↗

Effects of atropine and methacholine on deposition and clearance of inhaled particles in the donkey.

The influence of sympathetic and parasympathetic controls on regional particle deposition and mucociliary clearance rates was studied in the donkey in vivo. The deposition and clearance characteristics for gamma-tagged monodisperse ferric oxide microspheres were determined for inhalation tests after atropine and methacholine injections and were compared with the characteristics determined for control tests with the same animals and aerosols. Additional tests were performed in which methacholine was injected immediately after the test aerosol inhalation and 2 1/2 h before the particle inhalation. Particle deposition is shifted distally by atropine. Methacholine produces a proximal shift initially and a distal shift 2 1/2 h later. Atropine slows mucociliary transport. Methacholine produces an acceleration in bronchial clearance initially but causes a reduced rate of clearance 2 1/2 h later. Atropine slows mucociliary transport. Methacholine produces an acceleration in bronchial clearance initially but causes a reduced rate of clearance 2 1/2 h later. It also produces an initial surge in tracheal transport, which frequently leads to tracheal mucus refluxing and thereby an increase in average tracheal residence time. The drugs were used to modify the normal deposition and clearance characteristics of a particular animal so that they resembled the normal characteristics of a different animal, suggesting that much of the large intersubject variability may be attributable to different levels of autonomic tone.

Aerosols↗

Follow-up study of patients treated by X-ray epilation for tinea capitis: psychiatric and psychometric evaluation.

To investigate the late effects of radiation to the head upon subclinical mental disorders, a psychiatric and psychometric evaluation was performed on 177 cases treated 10-29 years earlier for ringworm of the scalp by X-ray therapy (N :109) or, by chemotherapy (N :68). Analyses which controlled for educational level and family psychiatric disorders showed that, among whites, the irradiated group manifested more psychiatric symptoms and more deviant MMPI (Minnesota Multiphasic Personality Inventory) scores. They were also judged more maladjusted from their MMPI profiles, and more frequently had a history of treated psychiatric disorders; however, the psychiatrist's overall rating of current psychiatric status showed only a borderline differnece between the two groups. There were no significant differences between irradiated and chemotherapy treated blacks.

Adult↗

Hepatic cell loss and proliferation induced by N-2-fluorenylacetamide, diethylnitrosamine, and aflatoxin B1 in relation to hepatoma induction.

Three hepatic carcinogens (aflatoxin B1, diethylnitrosamine (DEN) and N-2-fluorenylacetamide (FAA)) were compared for carcinogenicity, early cell toxicity and parenchymal cell proliferation. The carcinogens were administered to rats for 15 weeks as follows: aflatoxin B1, 1 in 10(6) in pelleted food; DEN, 2 in 10(5) in drinking water; FAA, 3 in 10(4) in pelleted food. The loss of prelabelled DNA and the [H3] TdR pulse-labelling indices (LI) of parenchymal and nonparenchymal cells were determined at various times during the period of carcinogen availability. On a molar basis, aflatoxin B1 was 90 times as carcinogenic as FAA and 24 times as carcinogenic as DEN. However, for about equal magnitudes of hepatic cell proliferation and loss, aflatoxin B1 was the least potent carcinogen. For a given level of carcinogenicity, FAA was more potent than DEN in causing loss of hepatic DNA and in increasing the parenchymal cell labelling index. DEN and aflatoxin B1 produced about the same degree of DNA loss and parenchymal cell labelling, but the former was a more potent carcinogen. When carcinogenicity was compared for approximately equal levels of early hepatic cell destruction and proliferation, the 3 chemicals in the present study could be ranked in descending order of potency as DEN, FAA and aflatoxin B1.

2-Acetylaminofluorene↗

Rationale developed by the Environmental Protection Agency for the assessment of carcinogenic risks.

The intent of the Environmental Protection Agency's "Interim Guideline for Carcinogen Risk Assessment" is to provide an evaluation of the evidence regarding suspect carcinogens that encapsulates judgments on the quality and adequacy of data, the likelihood that the agent is a human carcinogen, and an estimate of the magnitude of the cancer burden that could be ascribed to the agent if no regulatory action were taken. Every effort shoult be made to reduce environmental contamination by carcinogens to the lowest possible level; this view stems from uncertainties about qualitative and quantitative extrapolations from animals to man, the lack of evidence for a dose threshold, the great range of possible interactions among environmental carcinogens and cofactors, and the broad spectrum of human susceptibility. New knowledge in the field of carcinogenesis is developing, and modifications of the Environmental Protection Agency's "Interim Guideline for Carcinogen Risk Assessment" must be made periodically.

Carcinogens, Environmental↗

Breast neoplasms in women treated with x-rays for acute postpartum mastitis.

Breast cancer has been studied by mail survey up to 34 years in 571 of 606 women treated with x-rays for acute postpartum mastitis. The incidence of neoplasms was compared with that of three nonirradiated control groups--nonirradiated sisters of the treated women, women with acute postpartum mastitis not treated with X-rays, and their nonirradiated sisters. For the irradiated group, with mean dose of 247 rads to both breasts, the overall relative risk of breast cancer was 2.2 for years 10-34 post irradiation and 3.6 for years 20-34. The dose response for malignant and benign breast neoplasms was compatible with a linear fit. For comparable total doses, fractionation of exposure did not reduce carcinogenic action. Women over age 30 years at radiation treatment had as great an excess risk of breast cancer as did younger women. The overall excess risk of developing breast cancer was about 8-10 cases per million women per rad per year, an increase of about 0.5% per rad.

Adolescent↗

Occupational exposure to chloromethyl ethers. A retrospective cohort mortality study (1948-1972).

This industry-wide epidemiologic study to evaluate the human carcinogenicity of the chloromethyl ethers (CME) included 1827 CME-exposed workers and 8870 controls. Duration and relative intensity of exposure were classified by job description in the personnel records. This information permitted assigning relative magnitude of exposure scores for each job category at several plants, with allowance for temporal changes in the plant processes. Social security records were used for the ascertainment of deaths among separated employees. Death certificates were obtained for virtually all known deaths, and hospital pathology reports were obtained where possible for the cancer-related deaths. No differences in noncancer death rates were found. An increased risk of respiratory cancer death in CME-exposed workers was found at only one firm where high exposures are known to have occurred. A clear dose-response relationship with risk ratios exceeding ten for the longest duration and greatest exposure subgroups was demonstrated for this firm.

Bis(Chloromethyl) Ether↗

Effect of carcinogens on chicken atherosclerosis.

Weekly i.m. injections of the polycyclic hydrocarbon carcinogens, 7,12-dimethylbenz(a,h)anthracene (DMBA; 25 mg/kg/injection) and benzo(a)pyrene (50 mg/kg/injection) were given for a period of up to 22 weeks to chickens (SC strain) beginning at age 4 weeks. Atherosclerotic lesions of the abdominal aorta occurred more frequently and were larger in the DMBA- and benzo(a)pyrene-treated birds than in controls. These lesions were proliferative in character as indicated by a higher [3H]thymidine autoradiographic labeling index compared to the underlying medial cells of the aorta. Measurements of serum cholesterol in DMBA-treated birds showed no differences from controls. Although both carcinogens accelerated the development of atherosclerotic plaques, DMBA was more potent than benzo(a)pyrene.

9,10-Dimethyl-1,2-benzanthracene↗

Follow-up study of patients treated by x-ray epilation for tinea capitis. Estimation of the dose to the thyroid and pituitary glands and other structures of the head and neck.

This study is a further investigation of radiation dose to various head structures in the children given X-ray therapy for tinea capitis (ringworm of the scalp). In this work, estimates of the dose to the thyroid and pituitary gland were obtained with lithium fluoride thermoluminescent dosemeters using a child's head phantom. Doses were also measured for the parotid gland and several skin sites where skin tumours developed in the irradiated cases. In a previous study, brain and scalp doses of 140 and 500-800 rad had been estimated for the treated group using this same head phantom. In this work dosemeters were also placed in the same brain locations so that comparisons could be obtained between the two studies. The thyroid dose was estimated to be 6 +/- 2 rad and the pituitary dose was 49 +/- 6 rad for the conventional tinea capitis treatment. The dose to the parotid gland was 39 rad and the dose to skin sites on the face and neck where tumours occurred ranged from 20 to 40 rad. The data for the thyroid adenoma response from this and other studies involving irradiation of children suggests a linear dose-response relationship within the first 30-40 years after exposure with a risk of about 0-04% per rad.

Adenoma↗

Effect of adrenergic agents and their mode of action on mucociliary clearance in man.

The aerosolized adrenergic (ADR) agent, isoproterenol (ISO), was found markedly to accelerate mucus clearance within the human tracheobronchial tree. Mucus transport was measured by external gamma counting of aerosolized Fe2O3 particles deposited on the mucous membrane during inhalation. Aerosolized epinephrine (EPI), despite its alpha-ADR bronchial vasoconstrictor activity, increased mucus clearance to the same degree as did aerosolized ISO, with its beta-ADR bronchial vasodilator activity. The vehicle used for delivery of the ADR agents, i.e., a H2O aerosol by intermittent positive-pressure breathing (IPPB), itself increased mucus clearance slightly, but did not elicit the enormous increases produced by the ADR agents. Parenteral ISO caused increases in clearances similar to aerosolized ISO and EPI (consistent with different tissue drug levels achieved). Oral atropine delayed clearance, but atropine prior to an ADR aerosol did not alter the mucus transport effect of the ADR agent. ISO and atropine, despite opposite effects on mucus clearance, caused equal bronchodilation. Thus, increased clearance following aerosolized ISO was not dependent on bronchial vasodilation, aqueous aerosol droplets, reflex parasympathetic activation, or bronchodilation, and seems best attributable to increased ciliary beat rate.

Adult↗

Effect of pretest temperature on aerosol penetration and clearance in donkeys.

Pretest temperature and humidity were correlated with tracheobronchial particle penetration and clearance data from donkeys housed in unheated outdoor facilities and tested after spending 1-2 h in a temperature- and humidity-controlled laboratory. The animals inhaled an inert insoluble radioisotope-labeled monodisperse aerosol for several minutes. Its retention was monitored continuously for 3 h by external gamma detection. Aerosol deposition pattern and bronchial clearance were linearly correlated with pretest outdoor temperature which ranged from -10 to 30 degrees C. The fraction depositing in the unciliated regions of the lung decreased 0.6% per degrees C drop in outdoor temperature. Overall bronchial transport decreased at least 1.5% per degrees C decrease. Multiple linear regression analysis and correction for the positive correlation between temperature and humidity left no significant residual humidity dependence. Acclimatization of the animals in the laboratory for 6 h before testing significantly reduced these effects.

Aerosols↗

Assessment of environmental carcinogen risks in terms of life shortening.

An approach is presented to the assessment of carcinogen risks in which the dominant effect of carcinogen exposure is life shortening and the impact falls both on those individuals who would have gotten cancer without the carcinogen exposure as well as the new cancer cases. This analysis is based on the interaction of age-specific tumor incidence rates and population survival in terms of age-specific mortality rates without the induced risk from carcinogen exposure. The analysis yields estimates for lifetime probability of developing cancer, average lifespan lost by the entire population, the average age of cancer occurrence, and the average lifespan loss of cancer cases. The approach utilizes the animal response data to assign, to the existing human cancer occurrence, and equivalent dose of the same carcinogen which is under consideration in terms of risk evaluation. The approach has the advantages of keying the estimates of carcinogen risks to those which already exist in the environment, advoiding large extrapolations from animal data, and encompassing the variability in susceptibility and carcinogen exposure in humans.

Carcinogens↗

Regression kinetics of mouse skin papillomas.

The persistence and proliferation rate of mouse skin papillomas were studied in HA/ICR mice initiated with 7,12-dimethylbenz(a)anthracene and promoted three times weekly with phorbol myristate acetate. When the promoter treatments were stopped, rapid (half-time, 24 days) and slow (half-time, greater than 140 days) components of papilloma regression were observed. When the promoter dose was increased, the major effect was an increase among the rapidly regressing papillomas. Increases in the epidermal pulse-labeling index and the number of dermal inflammatory cells produced by phorbol myristate acetate in normal skin were reversible when the phorbol myristate acetate was stopped, but high pulse-labeling index values in papillomas were not reversible. Antithymocyte serum had no effect on regression, although ethylphenylpropriolate, a nonpromoting irritant, slowed the regression sufficiently to increase the half-time from 24 to 57 days. The action of the promoter in overcoming the regression tendency of the papillomas may explain certain features of the role of nonspecific irritation and the importance of promotion frequency in determining tumor yield.

9,10-Dimethyl-1,2-benzanthracene↗