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Biomedical subjects

A Aitio

Publications and source records attributed to A Aitio.

At least 55 records · Page 3Linked to original sources
PubMed1989

Metabolism of antipyrine and m-xylene in rats after prolonged pretreatment with xylene alone or xylene with ethanol, phenobarbital or 3-methylcholanthrene.

1. The metabolic disposition of antipyrine (AP) and m-xylene (XYL) has been studied in rats pretreated for a prolonged period with XYL, dosed alone or in combination with ethanol, phenobarbital (PB), or 3-methylcholanthrene (MC). 2. XYL inhalation exposure at 300 ppm in air (7 h/day, 4 days/week, for 1 or 4 weeks) did not alter the total 24-h recovery of AP and its major metabolites in urine, but the excretion profile changed compared with controls: 3-hydroxymethylantipyrine (3-HMA) increased (less than or equal to 14%, P less than 0.001), norantipyrine (NORA) (less than or equal to 23%, P less than 0.01) and AP (less than or equal to 53%, P less than 0.01) decreased. 4-Hydroxyantipyrine (4-OHA) was unchanged. 3. Oral dosage of XYL at 800 mg/kg per day (5 days/week, for 12 days) altered the metabolic disposition of AP similarly to inhalation. 4. XYL + ethanol did not alter the xylene-type effect on AP metabolism. This was at variance with the changes following XYL + PB and, to a greater extent, XYL + MC pretreatments: 4-OHA increased (53-74%, P less than 0.01), 3-HMA (11-42%, P less than 0.05) and AP (greater than or equal to 50%, P less than 0.05) decreased. The effect on NORA was less clear. 5. XYL pretreatment accelerated metabolic disposition of its major urinary metabolite, methylhippuric acid (MHA) and formation of thioethers. 6. Thioether excretion in 24 h urine was enhanced about 10-fold after XYL inhalation and 20-fold after oral administration. Only XYL + PB treatment enhanced further the excretion of xylene-derived thioethers (P less than 0.05). 7. Drug-metabolizing activity (phase I and II reactions) in liver, lung and kidney showed that the treatments resulted in marked and differential biochemical alterations. 8. In conclusion, m-xylene enhanced the rate of its own metabolism and induced differential changes on urinary AP metabolite profile depending on the pretreatment.

Administration, Inhalation↗
PubMed1988

Long-lasting effects of tobacco smoking on pulmonary drug-metabolizing enzymes: a case-control study on lung cancer patients.

Lung tissue specimens were taken during surgery from middle-aged men with either lung cancer (LC, n = 54) or a nonneoplastic lung disease (n = 20). Aryl hydrocarbon hydroxylase (AHH), 7-ethoxycoumarin O-deethylase (ECDE), epoxide hydrolase (EH), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities and glutathione and malondialdehyde contents were determined in 12,000 X g supernatant fractions from nontumorous parenchymal tissues. Interindividual differences in enzyme activities ranged from 11- to 440-fold, and glutathione content varied by 17-fold; the values showed unimodal distributions. AHH, ECDE, EH, and UDPGT activities were significantly and positively correlated to each other; a significant negative correlation was found between GST and the other enzymes. A relationship between enzyme activity and number of cigarettes smoked (pack-years) was found only for GST. Ignoring detailed smoking histories in the 6-month period preceding surgery, no difference was found in enzyme activities or glutathione content between LC and nonneoplastic lung disease patients or between smokers and nonsmokers. However, when the number of days since stopping smoking was considered, in smokers a significant increase was found for AHH, EH, and UDPGT activities and a significant decrease was found for GST activity, as compared to nonsmokers. LC patients who had smoked until the day before surgery had higher activities of AHH, ECDE, EH, and UDPGT than nonsmokers, while GST activity was reduced by one-third. The activities of these enzymes returned to the basal level found in nonsmokers within 59 (AHH), 108 (EH), 67 (UDPGT), and 40 (GST) days. LC patients who were recent smokers (within 30 days prior to surgery) had significantly induced AHH and ECDE activities when compared with smoking nonneoplastic lung disease patients. These results show that pulmonary drug metabolism can be altered by tobacco smoking and that these effects can last 40 to 108 days after cessation of smoking. These new findings should be considered in studies on the role of carcinogen-metabolizing enzymes in determining susceptibility to lung cancer.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1988

Evaluation of sister chromatid exchange as an indicator of sensitivity to N-ethyl-N-nitrosourea-induced carcinogenesis in rats.

Sister chromatid exchange (SCE) frequencies in peripheral lymphocytes are a frequently used endpoint to indicate exposures to genotoxins in groups of humans. The aim of this study was to ascertain, in an experimental design, whether or not SCE rates have any association with the risk of cancer at the individual level in rats exposed to a known carcinogen. Individual SCE rates were determined in three consecutive analyses in cultured blood lymphocytes of 50 adult male Wistar rats. Analyses were done before as well as 24 hr and 7 days after a single intraperitoneal administration of 0, 25, 50, or 75 mg/kg of N-ethyl-N-nitrosourea (ENU). The animals were followed until death; also, the relationship between SCEs and carcinogenic outcome, i.e., the presence or absence of tumors, and their latency period were examined. ENU significantly decreased the life expectancy of the rats. The tumor types most clearly associated with ENU treatment were various gliomas and thyroid-gland and testicular tumors. ENU induced a moderate (maximally 1.6-fold) increase in the mean frequency of SCEs/cell at both sampling times after treatment. The effect was somewhat more pronounced 1 day rather than 1 week after treatment. The mean SCE rates in rats with ENU-specific cancers or in animals with early or multiple tumors did not differ from those in animals that survived no less than 65 weeks or longer without developing tumors. In ENU-treated animals with tumors, no relationship was found between the mean SCE rate and survival time. It is concluded that in outbred Wistar rats the SCE response in cultured lymphocytes does not indicate individual susceptibility to the carcinogenic action of ENU. On a group basis, however, animals with high SCE rates were shown to have increased risk of cancer.

Animals↗
PubMed1988

Partial hepatectomy of rats ten weeks before carcinogen administration can enhance liver carcinogenesis: preliminary observations.

Partial hepatectomy (PH) is known to enhance liver carcinogenesis when it is performed several hours before or after administration of a hepatocarcinogen. This effect has been attributed to cell proliferation, which is induced by PH and is a necessary step for fixation of DNA damage leading to initiated cancer cells. We now report for the first time that PH can also increase the tumour incidence, and decrease the latency period, when it is performed 8-10 weeks before treating rats with the hepatocarcinogen N-nitrosodiethylamine. This animal model may offer a tool for investigating the underlying mechanism of the 'memory effect' and increased tumour susceptibility of liver cells after PH. Additionally, it could be explored as a more sensitive rodent bioassay for testing putative carcinogens.

Animals↗
PubMed1987

m-Xylene inhalation destroys cytochrome P-450 in rat lung at low exposure.

Rats were exposed to 0, 75, 150 or 300 ppm (1 ppm = 1 cm3/m3 = 4.35 mg/m3) m-xylene for 24 h and then killed. In the lungs, the cytochrome P-450 decreased to 45, 13 and 20% of the control value with the increasing exposure intensity and the activity of 7-ethoxycoumarin O-deethylase to 70, 27 and 14%, respectively. The activity of epoxide hydrolase increased slightly after exposures both at 150 (1.6-fold) and 300 cm3/m3 (1.4-fold), while the other measured drug-metabolizing enzyme activities showed no consistent changes. The non-protein sulfhydryl group content of the lungs was not affected. The concentrations of m-xylene in blood indicated that the solvent uptake increased in the different exposure groups more than expected, based on atmospheric concentrations alone. Morphologic studies of the lungs with scanning electron microscopy showed no apparent changes after exposure to 300 cm3/m3 or after a high oral dose (2 ml/kg/day, 3 days). Inhalation exposure to m-xylene for 5 weeks (7 h/day, 4 days/week) at a concentration of 300 ppm lowered the contents of cytochrome P-450 in rat lungs to 65% and the activity of 7-ethoxycoumarin O-deethylase to 41% without any other marked effects on the other drug-metabolizing enzymes or on the levels of non-protein sulfhydryl groups. In this study, the selective destruction of cytochrome P-450 in rat lung could be shown both after acute and subacute exposures and at concentrations low enough to warrant occupational concern.

Administration, Inhalation↗
PubMed1987

Analysis, storage stability and reference values for urinary chromium and nickel.

Simple direct dilution methods are described for the analysis of urinary chromium and nickel with electrothermal atomic absorption spectrometry. The day-to-day variation of the methods is in the order of 5%, and the detection limits 20 and 0.1 nmol/l (1.2 and 0.0052 micrograms/l) for urinary nickel and chromium, respectively. At levels corresponding to occupational exposures, both metals are stable (within 20%) in urine specimens in the refrigerator for the least ten months. The stability does not require acidification. Geometric mean values for urinary nickel and chromium in the non exposed population in Finland (n = 299 and 155) are 70 and 1.5 nmol/l (4.8 and 0.078 micrograms/l), and the upper 95% confidence limits from a log-normal distribution, are 170 and 11 nmol/l (10 and 0.57 micrograms/l), respectively.

Chromium↗
PubMed1986

Kinetics of 2,4,6-trichlorophenol in different organs of the rat.

The concentration of 2,4,6-trichlorophenol was measured in the blood and various other tissues of the rat after IP administration of the compound at 25 mg per kg body weight. The highest concentration, 329 +/- 117 nmol X g-1, was found in the kidney. Half-times were between 1.4 and 1.8 h in the blood, brain, fat, kidney, liver and muscle. The extent of conjugation of 2,4,6-trichlorophenol was also investigated by measuring total and free chlorophenol in the blood.

Animals↗
PubMed1986

Kinetics of the metal components of intratracheally instilled stainless steel welding fume suspensions in rats.

The kinetics of iron, chromium, nickel, and cobalt from manual metal arc and metal inert gas stainless steel welding fumes were studied. Neutron activated welding fumes, in aqueous suspensions, were instilled intratracheally into rats. The follow up continued for up to 106 days. From both fumes, approximately 10% of the injection bolus was immediately lost into the gastrointestinal tract, to be recovered in the faeces within three days. Thereafter, a pronounced difference was seen in the kinetics of the two types of fumes. After the first day, chromium, nickel, and iron were lost from the lungs with half times of about 53, 49, and 73 days after exposure to MMA/SS fumes, whereas practically no loss could be seen in the metal components of the metal inert gas welding fumes within two months. The disposition of chromium from MMA/SS fumes closely resembled that of intratracheally instilled water soluble chromates. On the other hand, the disappearance of trivalent chromium from MIS/SS fumes was considerably slower than that of the practically water insoluble chromates, or even of trivalent chromium salts. Thus the physical characteristics of the fume appreciably affect the kinetics of the clearance of chromium compounds from the lungs.

Animals↗
PubMed1986

Biological monitoring of nickel.

Measurements of nickel in body fluids, excreta, and tissues from humans with occupational, environmental, and iatrogenic exposures to nickel compounds are comprehensively reviewed. Correlations between levels of human exposures to various classes of nickel compounds via inhalation, oral, or parenteral routes and the corresponding concentrations of nickel in biological samples are critically evaluated. The major conclusions include the following points: Measurements of nickel concentrations in body fluids, especially urine and serum, provide meaningful insights into the extent of nickel exposures, provided these data are interpreted with knowledge of the exposure routes, sources, and durations, the chemical identities and physical-chemical properties of the nickel compounds, and relevant clinical and physiological information, such as renal function. Nickel concentrations in body fluids should not, at present, be viewed as indicators of specific health risks, except in persons exposed to nickel carbonyl, for whom urine nickel concentrations provide prognostic guidance on the severity of the poisoning. In persons exposed to soluble nickel compounds (e.g., NiCl2, NiSO4), nickel concentrations in body fluids are generally proportional to exposure levels; absence of increased values usually indicates non-significant exposure; presence of increased values should be a signal to reduce the exposure. In persons exposed to less soluble nickel compounds (e.g., Ni3S2,NiO), increased concentrations of nickel in body fluids are indicative of significant nickel absorption and should be a signal to reduce the exposures to the lowest levels attainable with available technology; absence of increased values does not necessarily indicate freedom from the health risks (e.g., cancers of lung and nasal cavities) associated with exposures to certain relatively insoluble nickel compounds.

Alloys↗
PubMed1985

Analysis of polychlorinated biphenyls (PCBs) in human serum.

Polychlorinated biphenyls (PCBs) are widely dispersed in the environment. Occupational exposure to PCBs takes place, e.g., in manufacture and repair of capacitors and transformers. A special type of exposure of workers to PCBs may occur in connection with accidents where capacitors or transformers containing PCBs products are damaged, as in the case of a fire or electric arcing. The quantitation of PCBs poses several problems: There are 209 different homologs and isomers of PCBs. The isomers of PCBs have different responses in the electron capture detector, and the pattern of PCBs in biological specimens is different from that of commercial products. In this study a method was worked out for the analysis of PCBs in serum with the purpose of estimating occupation exposure to PCBs. The PCBs were extracted to an organic solvent, and the extract was purified by use of sulfuric acid and silica columns. Capillary gas chromatography with electron capture detection was used. For separation, temperature programming was used.

Chromatography, Gas↗
PubMed1985

Metabolism of ethylbenzene in the rat during long-term intermittent inhalation exposure.

After exposure of rats to atmospheres of 50, 300 or 600 p.p.m. ethylbenzene six hours/day, five days/week, for a max. of 16 weeks, the concn. of ethylbenzene in perirenal fat and the urinary excretion of 1-phenylethanol, omega-hydroxyacetophenone, mandelic, phenylglyoxylic, hippuric and phenaceturic acids were measured at the second, fifth and ninth weeks. Excretion of metabolites into urine increased in a dose-related manner, but less than linearly. The level of exposure, but not the duration of exposure, markedly affected the pattern of the metabolites in the urine. The concn. of ethylbenzene in perirenal fat was low at 50 p.p.m., high at 300 p.p.m. and higher still at 600 p.p.m., but not in proportion to the increased dose.

Adipose Tissue↗