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W J Waddell

Publications and source records attributed to W J Waddell.

At least 19 recordsLinked to original sources
PubMed1992

Alcohol and cancer.

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Alcohol Drinking↗
PubMed1990

The distribution of [14C]acrylamide in rainbow trout studied by whole-body autoradiography.

The distribution of [2,3-14C]acrylamide was studied in fingerling rainbow trout by whole-body autoradiography. Fish weighing approximately 7 g were injected ip with 3.2 mg/kg [14C]acrylamide (0.1 microCi/g). One group of fish was kept in a fresh flowing water tank and frozen in dry ice/hexane 22 hr after injection; another group was placed in a separate tank of fresh flowing water and frozen 120 hr after treatment. A third group of fish served as nontreated controls. The autoradiographs of the fish at 22 hr show the highest concentration of radioactivity in the kidney, urinary bladder, blood, gallbladder, intestinal contents, and lens of eye. Lesser amounts of radioactivity are seen in the CNS, liver, and gills. Very low concentrations are seen in muscle. By 120 hr the only high concentrations are seen in gallbladder and lens of the eye. Lesser amounts are seen in the sclera, vertebrae, CNS, kidney, wall of intestine, and discrete spots in subcutaneous tissue presumed to be chromatophores. Low amounts are seen in muscle, the tissue usually consumed by man.

Acrylamide↗
PubMed1989

In vivo distribution of a carcinogenic hepatic peroxisome proliferator: whole-body autoradiography of [14C]ciprofibrate in the mouse.

The distribution of radiolabel in male mice was studied by whole-body autoradiography at intervals after oral administration of [14C]ciprofibrate, a carcinogenic hepatic peroxisome proliferator. Radioactivity was rapidly taken up by the liver and to a lesser extent by the brown fat within 9 h after oral dosing of ciprofibrate. The radioactivity levels in blood, interstitial fluid and fat decreased during the first 3 days after dosing, but the liver remained densely labeled. Between 3 and 27 days after dosing, liver exhibited a stippled pattern as a result of heavier labeling apparently around the central veins. The relatively low levels of radiolabel in extra-hepatic tissues observed after oral dosing, together with the prolonged retention in this region of the liver, is consistent with the hepatotropic effects (i.e. hepatic peroxisome proliferation and development of liver tumors) exerted by this compound.

Administration, Oral↗
PubMed1987

Inhibition of the localization of urethane in mouse tissues by ethanol.

[ethyl-1-14C]Urethane in water or in 12% ethanol was administered orally to male A/JAX mice and 1 hr later the mice were frozen and processed for whole-body autoradiography to identify sites of localization of radioactivity. When the [14C]urethane was administered in water, radioactivity was localized in the liver and bile, the salivary, seromucous and Harderian glands, the bone marrow and pancreas and the stomach and intestinal epithelia. When the labelled urethane was administered in 12% ethanol, localization of radioactivity in each of these sites was almost completely inhibited; radioactivity was still seen within the lumen of the stomach and intestine. Using a defined chemical system, no transesterification was observed between urethane and 12% aqueous [2H6]ethanol at pH 1.5 in 80 min. The inhibition of the localization of radioactivity in the tissues appears to be due most probably to blocking of the metabolism of urethane in tissues. This suggests that ethanol may inhibit the carcinogenicity of urethane in mice.

Animals↗
PubMed1986

The distribution of [14C]acrylamide in male and pregnant Swiss-Webster mice studied by whole-body autoradiography.

Male and 13.5- and 17.5-day pregnant Swiss-Webster mice were administered 120 mg/kg [2,3-14C]acrylamide orally. The male mice were frozen 0.33, 1, 3, 9, 24, 72, and 216 hr later, and the pregnant mice at each gestational period were frozen at 3 and 24 hr. Whole-body autoradiographs from the male mice at early time intervals revealed accumulation of radioactivity in the contents of the gastrointestinal tract, liver, pancreas, testis, brain and gallbladder, and epithelia of oral cavity, esophagus, and bronchi. The distribution appears to be similar in the male and pregnant mice. Absorption from the stomach was virtually complete by 3 hr; renal and hepatic elimination was essentially complete at 24 hr. Radioactivity in the male reproductive tract appeared in the parenchyma of the testis at 1 hr, moved to the seminiferous tubules and head of the epididymis at 9 hr, and by 9 days remained only in the tail of the epididymis and the crypts of the epithelium of the glans penis. This movement parallels that of spermatids. The 13.5-day fetuses were uniformly labeled except for a slightly increased uptake in fetal brain. The distribution of radioactivity in the 17.5-day fetal tissues resembled that in maternal tissues; the remarkable exception was an intense accumulation in fetal skin. This study indicates that acrylamide is efficiently absorbed from the stomach and eliminated by the liver, kidney, and possibly the pancreas. A previously unrecognized affinity of acrylamide or a metabolic product was demonstrated for fetal skin in late gestation and for adult epithelia of oral cavity, esophagus, forestomach, and bronchi. Also, acrylamide or a metabolite appears to bind to spermatids at a specific stage near maturation.

Acrylamide↗
PubMed1986

Disposition of [14C]dimercaptosuccinic acid in mice.

Dimercaptosuccinic acid labeled with 14C ([14C]DMSA) was administered to mice iv; the mice were frozen by immersion in dry ice/hexane at 6 and 20 min and 1, 3, 9, and 24 hr after injection. The frozen mice were sectioned and processed for whole-body autoradiography for soluble substances. The radioactivity was highly localized in extracellular fluids such as the subcutaneous, intrapleural, intraperitoneal, and periosteal spaces. There was a pronounced accumulation in the periosteal fluid above that in other fluids during the first hour after injection. Most of the radioactivity was eliminated by the kidney and liver. Pretreatment of a mouse with HgCl2 subcutaneously 1 hr before [14C]DMSA produced an increase in radioactivity in the liver and decrease in lung. A high concentration of radioactivity was seen at the subcutaneous site of injection of the HgCl2. The results are interpreted to indicate that most of the DMSA is in the extracellular space but that it can cross cellular membranes to some extent. The pronounced accumulation in periosteal fluid may be an interaction of DMSA with Ca2+ in this space. No tissue had a pronounced retention of the compound, but lung retained more than most other tissues.

Animals↗
PubMed1984

Histochemical localization of monoamine oxidase in whole-body, freeze-dried sections of mice.

Monoamine oxidase was investigated histochemically in tissues of the mouse by incubating freeze-dried, whole-body sections with tryptamine, serotonin, tyramine, beta-phenylethylamine, or benzylamine as substrate and Nitroblue tetrazolium as the final electron acceptor. The most intense staining with tryptamine was exhibited by intestinal epithelium and adrenal cortex; moderate staining was noted in the epithelium of the nose, bronchi, oesophagus, and upper stomach and in preputial gland, pancreas, nerve, spinal cord and brain. Weak staining was seen in the lung, spleen, liver and kidney. The distribution of the formazan deposition was similar, but much less intense, when serotonin and tyramine were used as the substrates. Only very weak staining was observed when beta-phenylethylamine was the substrate; no staining was seen with benzylamine. Monoamine oxidase activities with tryptamine were greatly inhibited by pretreatment with clorgyline (10 microM), while deprenyl (10 microM) slightly inhibited activities in all tissues except liver. This staining technique should be useful in further studies on the identification of the multiple forms of monoamine oxidase in tissues of the mouse. Nicotine and nitrosonornicotine were not substrates in any of the tissues; consequently, this enzyme system does not appear to produce the proximal carcinogen from this nitrosamine.

Adrenal Cortex↗
PubMed1984

Histochemical localization of primary and secondary alcohol dehydrogenases in whole-body, freeze-dried sections of mice.

Whole-body sagittal sections of frozen, C57BL/6J, adult, male mice were used for the localization of primary and secondary alcohol dehydrogenases in most tissues of the body. The reduction of Nitro BT with NAD+ as coenzyme, as described originally by Hardonk (1965), was utilized for the generation of coloured final reaction deposits. Ethanol was used as a substrate for primary alcohol dehydrogenase; 2-propanol, alpha-methylbenzyl alcohol and 2-butanol were used as substrates for secondary alcohol dehydrogenase. Liver and bronchial epithelium showed the highest activities for both enzymes; oesophageal and upper gastric epithelium showed a high activity of primary alcohol dehydrogenase. Pyrazole, indazole and imidazole inhibited primary, but not secondary, alcohol dehydrogenase. Dimethylsulphoxide and menthol slightly inhibited both enzymes. Oleic acid, sulphydryl agents, p-chloromercuribenzoate, and copper sulphate also inhibited both enzymes. Slight inhibition of secondary dehydrogenase was observed on co-administration of several alcohols. As expected, N-nitrosonornicotine did not function as a substrate for alcohol dehydrogenases. When this compound was present in the histochemical incubation media, no activity was seen at any of the usual sites of these enzymes. The distribution of the alcohol dehydrogenase activities found in this study correlates with the distribution of radioactivity in oesophagus, bronchi and liver after administration of [14C]nitrosonornicotine. This suggests that the alcohol dehydrogenases may be involved in the metabolism of hydroxylated nitrosonornicotine, a metabolite of the most abundant known carcinogen in cigarette smoke.

Alcohol Oxidoreductases↗
PubMed1984

The distribution of [14C]caprolactam in male, female and pregnant mice.

The distribution of [14C]caprolactam was studied by whole-body autoradiography in male, female and 14.5-day-pregnant mice. This technique does not allow translocation or removal of soluble compounds from the sites of localization. Pregnant mice were frozen 20 min and 1, 3, 9 and 24 hr after oral administration of the compound. The non-pregnant mouse was frozen 3 hr after oral dosing; two male mice were frozen 20 min and 9 hr after intravenous administration. Radioactivity was rapidly absorbed from the stomach and distributed throughout the entire animal, including the foetuses. There was efficient elimination by the kidney and liver. Material secreted by the liver into bile and intestinal contents appeared not to be reabsorbed via the enterohepatic circulation. The kinetics of distribution and elimination appeared to be the same in male, female and pregnant animals. The only sites of retention of radioactivity after 24 hr were the umbilical cords, amnion, yolk sac, maternal lens, maternal Harderian gland and maternal liver. The distribution into and removal from the foetuses was typical of molecules that diffuse freely across the placenta. There was no retention of radioactivity in any foetal tissue. With the possible exception of some residual activity in the nasal epithelium, no localization was seen that would suggest a site of toxic action of caprolactam.

Animals↗
PubMed1983

Inhibition by alcohols of the localization of radioactive nitrosonornicotine in sites of tumor formation.

Oral administration of ethanol, n-butanol, or t-butanol to mice 20 minutes before injection of carbon-14-labeled nitrosonornicotine inhibited the localization of radioactivity in bronchial and salivary duct epithelium and in the liver. Localization of radioactivity in the nasal epithelium and esophagus was not significantly reduced. These alcohols therefore may selectively inhibit tumor formation in three of the five sites where this carcinogen typically acts.

1-Butanol↗
PubMed1983

Affinity of [14C]nitrosopiperidine and metabolites for mouse epithelial tissues.

Male C57BL/6J mice were each administered iv 1.2 mg/kg (6.0 to 7.6 muCi) of [14C]nitrosopiperidine ([14C]NPIP) and frozen by immersion in dry ice/hexane at 0.1, 0.33, 1, 3, 9, and 24 hr after injection. The mice were processed for whole-body autoradiography without thawing or the use of any solvents; sagittal sections of the frozen mice were freeze-dried and placed on X-ray film to reveal areas of localization of radioactivity. The autoradiographs revealed intense localization of radioactivity at 6 min in the epithelium of the nose and bronchi, as well as in the liver, kidney, and salivary glands. There is virtually no affinity of [14C]NPIP for melanin. Most of the same localizations persisted from 6 min through 24 hr. At 24 hr the most intense accumulation was in the epithelium of the bronchi, nose, salivary gland ducts, and esophagus as well as the liver and Harder's gland. The results are interpreted to suggest that at least one metabolite of NPIP which localizes in the sites where tumors occur may be similar to a metabolite of NNN. The distribution is consistent with metabolic conversion of [14C]NPIP in liver and epithelium of nose and bronchi with subsequent localization of the metabolite in epithelium of esophagus and salivary gland ducts.

Animals↗
PubMed1983

Autoradiographic disposition of [1-methyl-14C]- and [2-14C]caffeine in mice.

Male, C57B1/6J mice received either [1-methyl-14C]caffeine or [2-14C]caffeine via the tail vein at a dose of 0.7 or 11 mg/kg, respectively. At 0.1, 0.33, 1, 3, 9, and 24 hr after treatment, the mice were anesthetized with ether and frozen by immersion in dry ice/hexane. The mice were processed for whole-body autoradiography by the Ullberg technique; this procedure does not allow thawing or contact with solvents. All autoradiographs revealed some retention of radioactivity at early time intervals in the lacrimal glands, seminal vesicle fluid, nasal and olfactory epithelium, and retinal melanocytes. The remaining portion of the animal was densitometrically uniform except for the lower levels noted in the CNS and adipose tissues. Excretion of radioactivity by the liver and kidneys seems to be the major routes of elimination. Localization in the liver at late time intervals was confined principally to the centrilobular region. Late sites of retention, observed only after [1-methyl-14C]caffeine administration, included the pancreas, minor and major salivary glands, splenic red pulp, thymal cortex, bone marrow, and gastrointestinal epithelium. Sites of localization present in both studies included the olfactory epithelium, lacrimal glands, hair follicles, and retinal melanocytes. Further studies are needed to determine whether the localization at these various sites is due to metabolic degradation, active transport, or possibly a specific receptor interaction.

Animals↗
PubMed1982

Carcinogenesis and nicotine in malignant melanoma of the choroid.

The most abundant carcinogen in tobacco smoke or its condensate has been identified as N-nitrosonornicotine. This is formed predominantly from nicotine in tobacco during curing and smoking but may also be generated within the body. Intravenous injection of 14C NNN appears highly concentrated in the choroid of pigmented mice. Like nicotine, it crosses the placental barrier and appears in the choroid of the embryonic eye in pregnant female mice. Other studies of the male melanoma population show a trend toward earlier life appearance of malignant melanoma in smokers and significantly less of disease-free melanoma-bearing males at five years among smokers. Immunoglobulin G and natural killer leukocyte activities appear to be reduced in male smokers with or without melanomas. Although species and strain differences in susceptibility to carcinogenic agents are well known, these findings led us to a retrospective analysis of 126 white adults undergoing enucleation as immediate therapy for unilateral malignant melanoma of the choroid between 1958 and 1978. Histologic verification and adequate follow-ups were obtained in 105 patients. Minimum follow-up in 65 survivors was 3 years and maximum was 24 years. In 40 patients with metastatic melanomas, death occurred at 3 months to 13 years or at an average of 44 months following surgery. An adequate history of tobacco use was obtained in 94 patients, 44 of which were positive for tobacco use (32 male; 12 female) and 50 were denials (16 male; 34 female). Questions to female patients or families of deceased women evoked more prompt and uncompromising denial than was experienced in questioning of male patients. Straight (non-actuarial) five year tumor mortality in white males with choroidal malignant melanoma showed 12 of 32 or 37% dead among male smokers and 1 of 13 or 8% dead among male non-smokers. Actuarial calculation of five year survival showed only 62% in tobacco using males and 85% in non-tobacco using males. The distribution of cytology was essentially similar in groups both by sex and other subgroupings. There were, however, more large tumors (greater than 10 mm in diameter) in the tobacco group (61%) vs the non-smokers (31%). These preliminary findings merit further analysis by prospective tobacco histories in malignant melanoma patients, particularly among the male population.

Adolescent↗