Flameless Atomic Absorption Spectrophotometry Research Articles

Mercury Distribution in the Neonatal and Adult Cerebellum after Mercury Vapor Exposure of Pregnant Squirrel Monkeys

The objectives of the study were (1) to map the detailed localization of mercury in the monkey cerebellum after mercury vapour exposure; (2) to investigate whether there is any difference in mercury distribution between neonatal and adult cerebellum after mercury vapor exposure; (3) to investigate the ability of mercury to accumulate in the cerebellum years after the end of exposure. Pregnant squirrel monkeys were exposed 5 days/week to mercury vapor at a concentration of 0.5 mg Hg/m3 air 4 or 7 h/day or 1 mg Hg/m3 air for 4 or 7 h/day. Mercury concentration in the offspring and maternal brains was examined by cold vapor, flameless atomic absorption spectrophotometry. Mercury distribution was examined by processing cerebellar sections for autometallographic (AMG) silver enhancement. Mercury concentration in the offspring cerebral occipital pole ranged between 0.20 and 0.70 μg Hg/g tissue, and in the maternal between 0.80 and 2.58 μg/Hg tissue in animals killed immediately after the end of exposure. AMG revealed that the external granule cell layer of offspring cerebellar tissue contained small amounts of mercury. The molecular layer contained mercury in some of the mercury-exposed monkeys. In the Purkinje cell layer, the Bergmann glial cells together with the Purkinje cells contained mercury. The granule cells and the Golgi cells contained small amounts of mercury. The astrocytes of the medullary layer, identified by immunohistochemistry, contained considerable amounts of mercury, but the cerebellar nuclei accumulated the highest amounts of mercury. No correlation was found between cellular accumulation and maturity of the brain; that is, the cellular localization of mercury did not differ between adult and neonatal brain, except for the amount of visualized mercury. This pattern corresponded well to the mercury concentrations found in the cerebral occipital pole. The differences found in mercury accumulation were instead considered to be dose-related. The results demonstrate that the distribution of mercury in the cerebellum after mercury vapor exposure is similar to the distribution pattern obtained after methyl mercury exposure and that mercury is trapped in the cerebellum over a long period of time.

Changes of lead levels in 24-h urine from 1985 to 1998 in Japanese adults

To determine whether current environmental lead (Pb) levels are causing any progressive changes in urinary Pb levels, 24-h urine samples were collected from 277 subjects (159 men and 118 women) in 1985, 312 subjects (155 men and 157 women) in 1993, and 311 subjects (156 men and 155 women) in 1998. All of the subjects worked in the same factory. The urinary Pb concentration was analyzed by flameless atomic absorption spectrophotometry. The geometric means for men were 4.74, 2.67 and 1.31 μg/day; 3.17, 1.78 and 1.04 μg/g creatinine; and 3.18, 1.99 and 0.98 μg/l urine in 1985, 1993 and 1998, respectively. The values for women were 3.22, 2.14 and 0.97 μg/day; 3.35, 2.26 and 1.15 μg/g creatinine; and 2.49, 1.86 and 0.83 μg/l urine, respectively. These results demonstrated that Pb levels in 24-h urine decreased significantly in the 13-year period ( P<0.01).

Antitumor activity of dextran derivatives immobilizing platinum complex (II).

The in vivo antitumor activity and toxicity of a newly synthesized polymeric prodrug of cisplatin was investigated and also compared with plain cisplatin. The prodrug included a dicarboxymethyl-dextran conjugate of cisplatin (DCM-Dex/CDDP). DCM-Dex/CDDP was i.v. injected in mice bearing s.c. Colon 26 mouse colon cancer cells. The tissue distribution of platinum was thereafter determined by flameless atomic absorption spectrophotometry. The platinic concentration of the organs showed a high rate of retention at 24 h after injection in the DCM-Dex/CDDP-treated mice. No biochemical or hematologically adverse effects were observed. In addition, DCM-Dex/CDDP showed a significantly higher antitumor activity than cisplatin alone. These results indicate that DCM-Dex/CDDP may therefore be a potentially effective cancer chemotherapy.

Changes in Trace Element Concentrations in Hair of Growing Children

Head hair concentrations of zinc, copper, manganese, alid iron from a total of 418 subjects (154 male and 264 female) aged between 6 mo and 20 yr were measured mainly with flameless atomic absorption spectrophotometry. Only zinc analysis of a part of the female samples (n = 140) were analyzed with inductively coupled plasmaatomic emission spectrometry. The two analytical methods showed close agreement. The mean concentration of copper and manganese were significantly higher in male subjects than in female subjects. The trace element concentrations in hair varied with the subject's age. Zinc concentration in hair decreased from 6 mo to 14 yr in the male subjects and decreased from 6 mo to 12 yr in the female subjects. Then, the concentrations increased gradually to 20 yr in the both sexes. Age-dependent variations of copper and manganese concentrations in hair showed similar trends to those of zinc. The results of this study suggest that a higher concentration in the diet of these trace elements may be required for growing children, especially in the period of adolescence.

DNA interactions of cisplatin tethered to the DNA minor groove binder distamycin.

Modifications of natural DNA in a cell-free medium using cisplatin tethered to the AT-specific, minor groove binder distamycin, were studied using various methods of biochemical analysis or molecular biophysics. These methods include: binding studies using differential pulse polarography and flameless atomic absorption spectrophotometry, mapping DNA adducts using a transcription assay, use of ethidium bromide as a fluorescent probe for DNA adducts of platinum, measurement of DNA unwinding by gel electrophoresis, measurement of CD spectra, an interstrand cross-linking assay using gel electrophoresis under denaturing conditions, measurement of melting curves with the aid of absorption spectrophotometry and the use of terbium ions as a fluorescent probe for distorted base pairs in DNA. The results indicate that attachment of distamycin to cisplatin changes several features of the DNA-binding mode of the parent platinum drug. Major differences comprise different conformational alterations in DNA and a considerably higher efficiency of the conjugated drug to form in DNA interstrand cross-links. Cisplatin tethered to distamycin, however, coordinates to DNA with similar base sequence preferences as the untargeted platinum drug. The results point to a unique profile of DNA binding for cisplatin-distamycin conjugates, suggesting that tethering cisplatin to minor groove oligopeptide binders may also lead to an altered biological activity profile.

Pharmacological studies of cisplatin encapsulated in long-circulating liposomes in mouse tumor models.

We investigated the pharmacokinetics and therapeutic efficacy of cisplatin encapsulated in polyethyleneglycol-coated long-circulating liposomes in a formulation referred to as SPI-077, in three mouse tumor models (M-109 lung carcinoma inoculated s.c., J-6456 lymphoma inoculated i.p. and A-375 melanoma inoculated s.c.). Tumor-bearing mice were injected i.v. with single doses of SPI-077 and cisplatin. For pharmacokinetic experiments, mice were sacrificed at different timepoints post-treatment. Platinum levels were determined in plasma, spleen, liver, kidneys and tumors using flameless atomic absorption spectrophotometry. Survival times and/or tumor size were recorded for therapeutic studies. The pharmacokinetic studies revealed a prolonged circulation time and enhanced tumor uptake for SPI-077. In contrast to these results, no superior antitumor activity of SPI-077 over cisplatin could be observed in all tumor models. In vitro release experiments showed a negligible release (below 10%) of platinum from the liposomes. An in vitro cytotoxicity assay indicated a reduced cytotoxic activity of SPI-077 in comparison to cisplatin. We concluded that SPI-077 is being delivered to the tumor sites in a low bioavailability form, with extremely slow release kinetics. This explains the discrepant results of high platinum concentrations in tumors and reduced therapeutic activity after administration of SPI-077.

Platinum distribution in malignant glioma following intraoperative intravenous infusion of carboplatin

The objective of this paper was to determine the time course and extent of platinum uptake into human malignant glioma tissue. An intraoperative, intravenous infusion of carboplatin was given to nine patients (seven glioblastoma and two anaplastic glioma) undergoing tumour excision. Carboplatin dosage was calculated individually to achieve a target systemic free carboplatin exposure.Tumour and peritumoural tissue was harvested at timed intervals following carboplatin administration. Plasma and tumour platinum concentrations were measured by graphite furnace flameless atomic absorption spectrophotometry. Histological examination was also performed on a piece of each tissue sample. The mean carboplatin dose administered was 783, SEM. 56 mg (range 485-903). Plasma pharmacokinetics showed a typical elimination curve. The mean peak plasma platinum concentration was 44, SEM 5 mug/ml (range 27-74).The mean total elemental plasma platinum area under the curve (AUC) was 9.0, SEM 1.4 mg/ml/min. Platinum was detected in 61 tumour samples, the mean peak concentration being 13 SEM 2 mug/g (range 5-21). Platinum was also detected in peritumoural brain and necrotic tumour. No correlation was apparent between the degree of necrosis in each tumour specimen and tumour platinum concentration. Platinum concentrations achieved in tumour were similar to levels that would be cytotoxic for glioma cells in vitro. The results of this study have implications for future studies using capillary permeability modifying agents as adjuncts to brain tumour chemotherapy.

Clinical Pharmacokinetics and Dose Optimisation of Carboplatin

Carboplatin shares some of the therapeutic advantages of cisplatin, but without a significant incidence of the dose-limiting neurotoxicity and nephrotoxicity which is experienced with cisplatin. However, its use is associated with dose-limiting bone marrow suppression. Carboplatin is present in the blood as 3 distinct species. These are total platinum and 2 unbound species, carboplatin itself and a decarboxylated platinum-containing degradation product. The 2 main methods used to assay the unbound species are flameless atomic absorption spectrophotometry and high performance liquid chromatography. The first of these methods assays both unbound platinum species, the second is specific for carboplatin. Both unbound species have similar pharmacokinetic profiles for the first 12 hours post-dose. Carboplatin appears to have a linear pharmacokinetic profile over the doses used clinically and does not interact significantly with drugs that are used commonly in combination chemotherapy. The pharmacokinetics of carboplatin are adequately described by an open 2-compartment model with elimination from the central compartment. Its clearance is proportional to the glomerular filtration rate and the volume of distribution of the central compartment appears to correlate with extracellular fluid volume. The elimination half-life varies with renal function and is typically between 2 and 6 hours in patients with a normal glomerular filtration rate and may be as long as 18 hours in patients with impaired renal function. Relationships between systemic exposure to carboplatin, described as the area under the concentration-time curve (AUC), and both toxicity and response have been described. For toxicity the strongest evidence exists for a relationship between AUC and thrombocytopenia. To a lesser extent the relationship between AUC and neutropenia has also been described. Patients already treated with platinum analogues have been shown to develop a greater degree of myelosuppression from any given AUC. In addition, some evidence suggests a relationship between the shape of the concentration-time curve and myelotoxicity, where constant infusions appear less likely to cause myelosuppression on a mg/m2 dose administration basis. The relationship between AUC and response rate is not as clear, this may be related to the lack of studies describing both the dose and AUC of carboplatin. There appears to be a more clearly defined AUC-response relationship for ovarian cancer than for other malignancies, with an AUC of between 5 and 7 mg/ml.min being associated with the maximal response rate [located at the plateau on an AUC-response curve]. However, new data suggest that higher AUCs may lead to greater response rates. Data from testicular cancer also strongly supports an AUC-response relationship with an increased number of treatment failures with carboplatin AUCs < 5 to 6 mg/ml.min. Given the AUC-effect relationships described above a number of studies have been performed to develop models to describe the relationship between both dose and AUC and dose and platelet nadir. In adults, perhaps the most common method is that of Calvert which describes the relationship between dose and AUC. Paediatric formulas have also been described. More recently a number of limited sampling strategies have been proposed as well as Bayesian dose individualisation techniques.

Biocompatibility of nickel‐titanium shape memory metal and its corrosion behavior in human cell cultures

Nickel-titanium alloy (Nitinol) is a metallic biomaterial that has a unique thermal shape memory, superelasticity, and high damping properties. Nitinol is potentially very useful in orthopedic surgery, for example. At present, there are not enough confirmative biocompatibility data available on Nitinol. The aim of our study was to clarify the primary cytotoxicity and corrosion rate of Nitinol in human cell cultures. Comparisons were made with stainless steel (Stst), titanium (Ti), composite material (C), and control cultures with no test discs. Human osteoblasts (OB) and fibroblasts (FB) were incubated for 10 days with test discs of equal size, 6 × 7 mm. The cultures were photographed and the cells counted. Samples from culture media were collected on days 2, 4, 6, and 8, and the analysis of metals in the media was done using flameless atomic absorption spectrophotometry. The proliferation of FB was 108% (Nitinol), 134% (Ti) (p < 0.02), 107% (Stst), and 48% (C)(p < 0.0001) compared to the control cultures. The proliferation of OB was 101% (Nitinol), 100% (Ti), 105% (Stst), and 54% (C) (p < 0.025) compared to the controls. Initially, Nitinol released more nickel (129–87 μg/L) into the cell culture media than Stst (7 μg/L), but after 2 days the concentrations were about equal (23–5 μg/L versus 11–1 μg/L). The titanium concentrations from both Nitinol and Ti samples were all <20 μg/L. We conclude that Nitinol has good in vitro biocompatibility with human osteoblasts and fibroblasts. Despite the higher initial nickel dissolution, Nitinol induced no toxic effects, decrease in cell proliferation, or inhibition on the growth of cells in contact with the metal surface. © 1997 John Wiley & Sons, Inc. J Biomed Mater Res, 35, 451–457, 1997.

Biocompatibility of nickel-titanium shape memory metal and its corrosion behavior in human cell cultures.

Nickel-titanium alloy (Nitinol) is a metallic biomaterial that has a unique thermal shape memory, superelasticity, and high damping properties. Nitinol is potentially very useful in orthopedic surgery, for example. At present, there are not enough confirmative biocompatibility data available on Nitinol. The aim of our study was to clarify the primary cytotoxicity and corrosion rate of Nitinol in human cell cultures. Comparisons were made with stainless steel (Stst), titanium (Ti), composite material (C), and control cultures with no test discs. Human osteoblasts (OB) and fibroblasts (FB) were incubated for 10 days with test discs of equal size, 6 x 7 mm. The cultures were photographed and the cells counted. Samples from culture media were collected on days 2, 4, 6, and 8, and the analysis of metals in the media was done using flameless atomic absorption spectrophotometry. The proliferation of FB was 108% (Nitinol), 134% (Ti) (p < 0.02), 107% (Stst), and 48% (C)(p < 0.0001) compared to the control cultures. The proliferation of OB was 101% (Nitinol), 100% (Ti), 105% (Stst), and 54% (C) (p < 0.025) compared to the controls. Initially, Nitinol released more nickel (129-87 micrograms/L) into the cell culture media than Stst (7 micrograms/L), but after 2 days the concentrations were about equal (23-5 micrograms/L versus 11-1 micrograms/L). The titanium concentrations from both Nitinol and Ti samples were all < 20 micrograms/L. We conclude that Nitinol has good in vitro biocompatibility with human osteoblasts and fibroblasts. Despite the higher initial nickel dissolution, Nitinol induced no toxic effects, decrease in cell proliferation, or inhibition on the growth of cells in contact with the metal surface.

Catalytic analysis of trace manganese(II) using stilbazo in the presence of ethylenediamine and hydrogen peroxide.

Catalytic analysis of trace manganese using Stilbazo has been investigated in the presence of ethylenediamine and hydrogen peroxide. Stilbazo was decomposed by the hydroxy radical formed with hydrogen peroxide in the presence of trace Mn(II). The reaction rate was enhanced by ethylenediamine, which acts as an activator in addition to a masking agent. The concentration of Mn(II) was estimated by measuring the decrease in the absorbance of Stilbazo(S). The absorbances of Stilbazo were measured at the start and then t minutes after the reaction-start, respectively. The relation between [S]t and [Mn2+] is ln[S]t= -k [Mn2+]t, +ln[S]0. Here, [S]0 and [S]t denote the concentrations of Stilbazo at the initial state and, then t minutes after reaction-start. In the above, k is the apparent reaction rate constant. This reaction was considered to be pseudo-first order regarding S. A calibration curve showed linearity over the range 01.2 ppb at t=5. The detection limit of Mn(II) by the proposed method was 10 ppt. This method was applied to tap-water samples. The results showed good agreement with the values obtained from flameless atomic-absorption spectrophotometry. Diverse ions (Ca(II), Co(II), Cr(III), Cu(II), Ni(II), Ti(IV) and V(V)) did not interfere with the determination of Mn(II) at 0.8 ppb. On the other hand, Fe(III), Zn(II) and Al(III) interfered with the determination of Mn(II) in the presence of more than 50-fold the Mn(II) concentration.

Lead concentrations in lichens from the Canadian high arctic in relation to the latitudinal pollution gradient

Measuring deposition of anthropogenic Pb is essential for quantifying global patterns of pollution dispersion. Concentrations of Pb, however, have only rarely been measured in lichens collected from the High Arctic. In this study we used flameless atomic absorption spectrophotometry to determine that the average Pb content in five lichen species from several remote sites on Ellesmere Island was 2 µg g−1 dry wt. These are among the lowest Pb concentrations that have ever been recorded in Arctic plants. Literature data were combined to establish a latitudinal gradient showing decreasing Pb concentrations in lichens with increasing latitude throughout Canada.

Carboplatin dosing based on measurement of renal function--experience at the Peter MacCallum Cancer Institute.

Carboplatin is used in treating many types of cancer. Because renal excretion is the major variable determining the pharmacokinetics of this drug, a dosing formula based on glomerular filtration rate (GFR) has been proposed and is being increasingly used in carboplatin dosing. This method of dosing is critically dependent on accurate measurement of GFR. To report the experience at a single major oncology centre of carboplatin dosing based on GFR, and comparisons of different methods of measuring renal function for use in this dosing method. An initial group of patients (n = 24) was studied where GFR was measured by Cr51EDTA clearance and compared to Tc99mDTPA clearance, measured 24 hour urine creatinine clearance and the Cockcroft and Gault formula. The carboplatin area under the plasma concentration versus time curve (AUC) was calculated using total platinum measured in a single blood sample assayed by flameless atomic absorption spectrophotometry. A subsequent patient group (n = 16) was then studied using Tc99mDTPA clearance to measure GFR. Carboplatin dosing using Cr51EDTA clearance to measure GFR was accurate (< 25% difference between planned and measured AUC) in 87% of samples. Estimation of renal function using the Cockcroft and Gault formula correlated with Cr51EDTA clearance only in patients with GFR < 100 mL/minute. The measured 24 hour urine creatinine clearance did not correlate with Cr51EDTA clearance. Using Tc99mDTPA clearance to measure GFR, carboplatin dosing was accurate in 81% of samples. Across a GFR range of 42-239 mL/minute, the Cr51EDTA and Tc99mDTPA clearance were closely correlated (r = 0.98, slope of regression line = 1.02). Carboplatin dosing using a pharmacological formula based on GFR produces accurate targeting of the carboplatin AUC. Tc99mDTPA clearance can be used to measure GFR instead of Cr51EDTA clearance, which is both more convenient and has potential cost savings. Estimates of renal function using the Cockcroft and Gault formula or measured 24 hour creatinine clearance are insufficiently accurate to use for carboplatin dosing.

Lack of topographical relationship between sites of aluminum deposition and senile plaques in the Alzheimer's disease brain.

Aluminum has been presumed to be involved in the pathogenesis or etiology of Alzheimer's disease. Histochemical demonstration of aluminum in autopsy brains from Alzheimer's disease victims by means of the solochrome azurine method in combination with the methenamine silver technique revealed aluminum-related staining in some neocortical and hippocampal senile plaques and tangles, as well as in the cytoplasm and/or the nuclei of some neurons, and in the cytoplasm of endothelial cells of blood capillaries and pericytes around larger blood vessels. In double-stained samples (first with methenamine silver and then with solochrome azurine) only some plaques displayed the presence of aluminum, while others did not show any sign of the presence of the trace metal. The specificity and sensitivity of solochrome azurine staining was checked in paper spot-test and test-tube experiments combined with flameless atomic absorption spectrophotometry. The results suggest that aluminum is present in brain samples from Alzheimer's disease victims, but the structural localization indicates that it is not primarily involved in the etiology of the disease.

Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin

We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours.

Hepatic Concentrations of Zinc, Copper and Manganese in Infants with Extrahepatic Biliary Atresia

The objective of this study was to determine the concentration of Zinc (Zn), Copper (Cu) and Manganese (Mn) in hepatic tissue from extrahepatic biliary atresia (EHBA). Liver biopsy samples were obtained at time of portoenterostomy from 49 infants ages 1.1 to 20.7 months (median 2.1) with EHBA. Samples were dry ashed and analyzed by flame (Zn) or flameless (Cu and Mn) atomic absorption spectrophotometry. Hepatic Cu concentrations are physiologically elevated at birth and decline rapidly during the first 2 month of life, therefore only samples from 29 infants, ages greater than 8 weeks were considered for Cu. Concentrations (mg/kg dry weight, mean and range) were: Zn 142 (70-507), Cu 204 (19-570), Mn 9.1 (2.8-21.8) vs. literature controls in the same age range: Zn 262 (82-543), Cu 92, Mn 4.3 (3.3-11.5). No correlations were found between serum alkaline phosphatase, AST or total bilirubin and hepatic trace element concentrations, between trace element concentrations and age, or between Cu and Mn. Decreased bile flow with intrahepatic cholestasis may result in hepatic accumulation of Mn as well as Cu. The low hepatic Zn concentrations indicate the need for further study of Zn metabolism in this population.

Skin uptake, distribution, and elimination of antimony following administration of sodium stibogluconate to patients with cutaneous leishmaniasis.

We examined in this study the pharmacokinetics of Sb in the affected skin and normal skin of patients treated with sodium stibogluconate for cutaneous leishmaniasis and compared the results with those for the blood. The procedure was fully explained, and a written consent was obtained from each of nine patients. After a dose of sodium stibogluconate equivalent to 600 mg of Sb was administered intramuscularly, small skin biopsies were collected under local anesthesia at different time intervals from the circumferences of the lesions and simultaneously from normal skin. Antimony was measured in these biopsies after suitable ashing and processing by flameless atomic absorption spectrophotometry. The means (with standard errors of the means in parentheses) of the peak concentration, time to peak concentration, area under the curve, half-life, and mean residence time in lesions were 5.02 (1.43) micrograms/g, 2.1 (0.4) h, 32.8 (6.1) micrograms.h/g, 6.88 (0.54) h, and 10.4 (1.2) h, respectively, and those in normal skin were 6.56 (2.01) micrograms/g, 2.6 (0.8) h, 44.0 (15.8) micrograms.h/g, 5.44 (0.83) h, and 8.08 (1.34) h, respectively. There was no significant difference in any of these parameters between lesions and normal skin, whereas the differences in peak concentration, half-life, and mean residence time between lesions and whole blood were significant (P < or = 0.05). The penetration of Sb into skin, either affected or normal, as measured by the skin/blood area under the curve ratio appears to be complete, but the disposition is slow compared with that from the blood.

Determination of butyltin metabolites in the mouse liver by flameless atomic absorption spectrophotometry.

A new analytical method for observation of the metabolic status of butyltin compounds in the mouse liver was devised by a combination of extraction, purification and separation followed by quantitative analysis of each butyltin compound. After the extraction of all tin compounds from liver homogenate with ethyl acetate, these compounds were purified by combination of the fractional extract with organic solvents and column chromatography. The purified fraction was also analyzed by thin-layer chromatography, identifying each tin compound from differences in mobility on a silica gel plate. The tin content in the each separated spot on the plates was measured by flameless atomic absorption spectrophotometry after extraction by acid treatment. About 90% of tin was recovered by this method from the liver of mice which had been administered tri- or dibutyltin compound orally. This method will be useful for quantification of each metabolic product formed from butyltin compounds in vivo.

Pharmacokinetics and antitumor activity of a new platinum compound,cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl- 1, 3-dioxolane]platinum(II), as determined by ex vivo pharmacodynamics

The pharmacokinetics and ex vivo pharmacodynamics studies on cis-malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1, 3- dioxolane]platinum(II) (SKI 2053R, NSC D644591), cisplatin (CDDP), and carboplatin (CBDCA) were performed in beagle dogs. Equitoxic doses of SKI 2053R, CDDP, and CBDCA (7.5, 2.5, and 15.0 mg/kg, respectively) were given by i.v. bolus to three beagle dogs in a randomized crossover study. Plasma samples were analyzed for platinum by flameless atomic absorption spectrophotometry. Plasma concentrations of total and ultrafiltrable platinum for the three drugs declined in a biexponential fashion. The mean area under the concentration-time curve (AUC0-->infinity) determined for ultrafiltrable platinum derived from SKI 2053R, as an active component, was 7.72 +/- 2.74 micrograms h ml-1 (mean +/- SD), with an initial half-life of 0.37 +/- 0.20 h, a terminal half-life of 2.19 +/- 0.93 h, a total clearance of 16.83 +/- 4.76 ml min-1 kg-1, and a steady-state volume of distribution of 1.57 +/- 0.30 l/kg. The ex vivo antitumor activity of SKI 2053R was assessed using the ultrafiltrable plasma against two human lung-adenocarcinoma cell lines (PC-9 and PC-14) and five stomach-adenocarcinoma cell lines (MKN-45, KATO III, SNU-1, SNU-5, and SNU-16) by tetrazolium-dye (MTT) assay and was compared with that of CDDP and CBDCA using an antitumor index (ATI) determined from the ex vivo pharmacodynamic results of inhibition rates (%) versus time curves. The mean ATI value was shown to be ranked in the following order: SKI 2053R > CBDCA > CDDP. The mean ATI values recorded for SKI 2053R and CBDCA were significantly (P < 0.05) higher than that noted for CDDP; however, no statistically significant difference was observed between SKI 2053R and CBDCA, suggesting that the antitumor activity of SKI 2053R is superior to that of CDDP and is equivalent to that of CBDCA. These results suggest that SKI 2053R is a promising candidate for further development as a clinically useful anticancer drug.

Concentration of mercuryin hair of Japanese people

This investigation was made to estimate current normal concentrations of total mercury in the hair of Japanese people. Hair samples were collected from 365 healthy volunteers in Tokyo and the surrounding areas from June 1992 to June 1993. Mercury contents in the samples were analyzed by gold amalgam flameless atomic absorption spectrophotometry. The mean of the concentrations of total mercury in the hairs of the males(2.98 ppm,81 volunteers with an average age of 34.7, age 11 to 73) was higher than that of the females(2.02 ppm, 284 volunteers with an average age of 26.5, age 12 to 82). In both the male and female, the mean of the concentrations of total mercury in hair increased with age up to their thirties,then gradually decreased. The concentrations of total mercury in the hair of females at age 18 to 40 showed greater fluctuation, as compared to those of males in the same age groups. In both males and females, the concentration of total mercury in the hair was higher in volunteers who have a preference to fish in their diet than in those who prefer other foods. In both males and females, there was no positive correlation between the total hair mercury and the place of residence of the volunteer although the total hair mercury (2.30 ppm) of male volunteers who inhabit Ibaragi and Chiba, in eastern part of Tokyo, facing the Pacific Ocean or both the Pacific Ocean and Tokyo Bay, was lower than those(3.30 and 3.25 ppm) of male volunteers of other two areas. The mean concentration of total mercury in the hair obtained from all the volunteers was 2.23 ppm, which is considerably lower than that (6.02 ppm) from 73 healthy inhabitants of the same areas in the early 1960's. It is speculated from these results that a major current route for mercury exposure in the Japan is fish consumption.