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Biomedical subjects

G L Li

Publications and source records attributed to G L Li.

At least 73 records · Page 4Linked to original sources
PubMed1992

S-phenylcysteine formation in hemoglobin as a biological exposure index to benzene.

Benzene is metabolized to intermediates that bind to hemoglobin, forming adducts. These hemoglobin adducts may be usable as biomarkers of exposure. In this paper, we describe the development of a gas chromatography/mass spectroscopy assay for quantitating the binding of the benzene metabolite, benzene oxide, to cysteine groups in hemoglobin. We used this assay to study the hemoglobin adduct, S-phenylcysteine (SPC), in the blood of rats and mice exposed to benzene either by inhalation or by gavage. We were able to detect SPC in the hemoglobin of exposed rats and mice, to show the linearity of the exposure dose-response relationship, and to establish the sensitivity limits of this assay. For the same exposure regime, rats showed considerably higher levels of SPC than did mice. As yet, we have not been able to detect SPC in the globin of humans occupationally exposed to benzene. We attempted to determine whether the SPC found in hemoglobin originated from the metabolism of benzene within or outside of the red blood cell. We hypothesized that the greatest red blood cell metabolism would be associated with peripheral reticulocytes, which retain high metabolic capacity. After exposing rats to benzene, we isolated the red blood cells and used discontinuous Percoll gradients to fractionate them into age groups. No differences in SPC levels were found among any of the fractions, suggesting that the SPC found in globin originates from the metabolism of benzene to benzene oxide in a location external to the red blood cell. To our knowledge, this is the first demonstration of the nonenzymatic binding of the benzene metabolite, benzene oxide, to protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Muconic acid determinations in urine as a biological exposure index for workers occupationally exposed to benzene.

Urinary phenol determinations have traditionally been used to monitor high levels of occupational benzene exposure, but the same technique cannot be used to monitor low-level exposures because of the high background of phenol resulting from its presence in many foods and from metabolism of aromatic amino acids. Thus, new biological indexes for exposure to low levels of benzene are needed. Animal studies indicate that muconic acid is a metabolite of benzene that is excreted in the urine as an increasing fraction of the total benzene metabolites with decreasing dose of benzene. Thus, urinary muconic acid is potentially useful as a monitor for low levels of exposure to benzene. It is also of interest to determine the level of muconic acid in the urine of humans exposed to benzene for comparison with animal data as an aid for use of the animal studies in risk assessments for humans. This report describes the development of a gas chromatography/mass spectrometry assay to detect and quantitate the benzene metabolite, muconic acid, in urine. The internal standard used in the assay, muconic acid-d4, was biosynthesized by F344/N rats administered benzene-d6 by gavage; the muconic acid was isolated from the rat's urine. Muconic acid was measured in experimental urine samples by adding the internal standard, followed by extraction and derivatization. Phenol was also measured in urine after extraction and derivatization. The assays were applied to the urine samples from 14 workers occupationally exposed to benzene and 8 workers with no known benzene exposure. Muconic acid could be detected in all of the urine samples at levels greater than 100 ng/mL.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Induction of the L forms of M. tuberculosis in vivo guinea pigs].

The cell suspension of M. tuberculosis H37Rv was injected into guinea pigs by nares and intraperitoneal, respectively. It was found that the L forms were induced in lungs of guinea pigs the third week after the infection intranasally and the second week after the infection intraperitoneally. The numbers of the L form colonies induced by two infection passage were the highest the eighth week after the infection. There was a decrease in the numbers of bacilli when the numbers of the L forms isolated from lungs increased strikingly. The presence of the L forms was demonstrated directly by electron microscope. The findings suggest that the L forms are easily induced and may be persist for long time in vivo. There is a certain relationship between the induction of the L forms and bacilli dynamic changes.

Animals↗
PubMed1989

Relationship between vapor exposure and urinary metabolite excretion among workers exposed to trichloroethylene.

The exposure-excretion relationship was investigated in 140 trichloroethylene (TRI)-exposed workers and 114 nonexposed controls. The time-weighted average intensity of exposure to TRI during the shift as measured by the diffusive sampling method was compared with metabolite levels in the urine collected at the end of the shift in the second half of a working week, when the urinary metabolite levels are expected to reach a maximum. The TRI levels in breathing zone air of the exposed workers were mostly below 50 ppm. The urinary metabolite levels (i.e., total trichloro-compounds, trichloroethanol, and trichloroacetic acid) increased as a linear function of the TRI exposure. The relationship between the two exposure indicators was statistically significant in men, women, and both combined. The cross-sectional balance study at the end of the shift revealed that about 4% of TRI absorbed will be excreted at the end of the shift, in agreement with the long biological half-life of this chlorinated hydrocarbon solvent. A possible ethnic difference in the metabolism of TRI is discussed.

China↗
PubMed1989

Urinary t,t-muconic acid as an indicator of exposure to benzene.

A method for rapidly determining t,t-muconic acid (MA) by high performance liquid chromatography was developed and successfully applied to urine samples from 152 workers exposed to benzene (64 men, 88 women) and 213 non-exposed controls (113 men, 100 women). The MA concentrations in urine correlated linearly with time weighted average benzene concentrations in the breath zone air of workers. A cross sectional balance study showed that about 2% of benzene inhaled is excreted into the urine as MA. The MA concentrations in the urine of the non-exposed was below the detection limit (less than 0.1 mg/l) in most cases, and the 95% lower confidence limit of MA for those exposed to benzene at 5 ppm (5.0 mg/l as a non-corrected value) was higher than the 97.5%-tile values for the non-exposed (1.4 mg/l). In practice, it was possible to separate those exposed to 6-7 ppm benzene from the non-exposed by means of urine analysis for MA. The urinary MA concentration was suppressed by coexposure to toluene.

Air Pollutants, Occupational↗
PubMed1989

Excretion of 1,2,4-benzenetriol in the urine of workers exposed to benzene.

Urine samples were collected from 152 workers (64 men, 88 women) who had been exposed to benzene, 53 workers (men only) exposed to a mixture of benzene and toluene, and 213 non-exposed controls (113 men, 100 women). The samples were analysed for 1,2,4-benzentriol (a minor metabolite of benzene) by high performance liquid chromatography. The time weighted average solvent exposure of each worker was monitored by diffusive sampling technique. The urinary concentration of 1,2,4-benzentriol related linearly to the intensity of exposure to benzene both in men and women among workers exposed to benzene, and was suppressed by toluene co-exposure among male workers exposed to a mixture of benzene and toluene. A cross sectional balance study in men at the end of the shift of a workday showed that only 0.47% of benzene absorbed will be excreted into urine as 1,2,4-benzenetriol, in close agreement with previous results in rabbits fed benzene. The concentration of 1,2,4-benzenetriol in urine was more closely related to the concentration of quinol than that of catechol. The fact that phenol and quinol, but not catechol, are precursors of 1,2,4-benzentriol in urine was further confirmed by the intraperitoneal injection of the three phenolic compounds to rats followed by urine analysis for 1,2,4-benzenetriol.

Animals↗
PubMed1989

A retrospective cohort study of leukemia and other cancers in benzene workers.

A retrospective cohort study was carried out in 1982-1983 among 28,460 benzene-exposed workers (15,643 males, 12,817 females) from 233 factories and 28,257 control workers (16,621 males, 12,366 females) from 83 factories in 12 large cities in China. All-cause mortality was significantly higher among the exposed (265.46/100,000 person-years) than among the unexposed (139.06/100,000 person-years), as was mortality from all malignant neoplasms (123.21/100,000 versus 54.7/100,000, respectively). For certain cancers, increased mortality was noted among benzene-exposed males in comparison with that among unexposed males; the standardized mortality ratios (SMR) were elevated for leukemia (SMR = 5.74), lung cancer (SMR = 2.31), primary hepatocarcinoma (SMR = 1.12), and stomach cancer (SMR = 1.22). For females only leukemia occurred in excess among the exposed. Risk of leukemia rose as duration to exposure to benzene increased up to 15 years, and then declined with additional years of exposure. Leukemia occurred among some workers with as little as 6 to 10 ppm average exposure and 50 ppm-years (or possibly less) cumulative lifetime exposure (based on all available measurements for the exposed work units). Among the 30 leukemia cases identified in the exposed cohort, the proportion of subjects with acute lymphocytic leukemia was substantially lower and the proportion with acute nonlymphocytic leukemias was higher than in the general population. During 1972 to 1981, the annual incidence of leukemia ranged from 5.83 to 28.33 per 100,000 with higher rates occurring in the interval 1977 to 1981 than in the earlier years of the study period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

[Synthesis of some halogenated indirubin derivatives].

Indirubin has been used clinically to treat chronic granulocytic leukemia, but poor solubility limited its absorption in the body. In order to reduce its side effect and raise its therapeutic effect on chronic granulocytic leukemia, six halogen-substituted derivatives were synthesized. Compounds I, II, III and V exhibited higher antitumor activity against L7212 bearing mice and W256 bearing rats than indirubin. In the parallel experiment, the most active compound III showed increase in life-span of mice bearing L7212 by 41-73%, and marked inhibitory action against W256 in rats with the inhibition rates of 48-83%, while indirubin showed 0 and 30% inhibition.

Animals↗
PubMed1988

Mutual metabolic suppression between benzene and toluene in man.

The exposure intensity during a shift and the metabolite levels in the shift-end urine were examined in male workers exposed to either benzene (65 subjects; the benzene group), toluene (35 subjects; the toluene group), or a mixture of both (55 subjects; the mixture group). In addition, 35 non-exposed male workers (the control group) were similarly examined for urinary metabolites to define background levels. A linear relationship was established between the intensity of solvent exposure and the corresponding urinary metabolite levels (i.e. phenol, catechol and quinol from benzene, and hippuric acid and o-cresol from toluene) in each case when one of the three exposed groups was combined with the control group for calculation. Comparison of regression lines in combination with regression analysis disclosed that urinary levels of phenol and quinol (but not catechol) were lower in the mixture group than in the benzene group when the intensities of exposure to benzene were comparable, indicating that the biotransformation of benzene to phenolic compounds (excluding catechol) in man is suppressed by co-exposure to toluene. Conversely, metabolism of toluene to hippuric acid was suppressed by benzene co-exposure. Conversion of toluene to o-cresol was also reduced by benzene, but to a lesser extent. The significance of the present findings on the mutual suppression of metabolism between benzene and toluene is discussed in relation to solvent toxicology and biological monitoring of exposure to the solvents.

Air Pollutants, Occupational↗
PubMed1988

Determination of catechol and quinol in the urine of workers exposed to benzene.

Time weighted average concentrations of benzene in breathing zone air (measured by diffusive sampling coupled with FID gas chromatography) and concentrations of catechol and quinol in the urine (collected at about 1500 in the second half of a working week and analysed by high performance liquid chromatography) were compared in 152 workers who were exposed to benzene (64 men, 88 women). The concentration of urinary metabolites was also determined in 131 non-exposed subjects (43 men, 88 women). There was a linear relation between the benzene concentrations in the breathing zone and the urinary concentrations of catechol and quinol (with or without correction for urine density) in both sexes. Neither catechol nor quinol concentration was able to separate those exposed to benzene at 10 ppm from those without exposure. The data indicated that when workers were exposed to benzene at 100 ppm about 25% of benzene absorbed was excreted into the urine as phenolic metabolites, of which 13.2%, 1.6%, and 10.2% are phenol, catechol, and quinol, respectively.

Benzene↗
PubMed1988

Increased subjective symptom prevalence among workers exposed to trichloroethylene at sub-OEL levels.

Over 100 workers exposed to trichloroethylene (TRI) mostly at less than 50 ppm during the production or vapor degreasing operation and about an equal number of the non-exposed control workers were examined for subjective symptoms, hematology, serum biochemistry, and sugar, protein and occult blood in urine. Essentially all the clinico-laboratory tests stayed normal, and there was no significant differences in the findings between the exposed and the controls. Thus, no clinically significant effects of TRI exposure were found in the blood and liver functions among the exposed workers as compared with the controls. The prevalence of the subjective symptoms was, however, significantly higher in the exposed group than in the controls, and dose-response relationship could be established in some selected symptoms such as nausea, heavy feeling in the head, forgetfulness, tremor in extremities, cramp in extremities and dry mouth, although the exposure was low. The findings warrant further attention to the effects of TRI especially on the central nervous system at the concentration lower than e.g., 50 ppm.

Adult↗
PubMed1987

Leukaemia in benzene workers: a retrospective cohort study.

A retrospective cohort study was conducted in 233 benzene factories and 83 control factories in 12 cities in China. The benzene cohort and the control cohort consisted of 28,460 benzene exposed workers (178,556 person-years in 1972-81) and 28,257 control workers (199,201 person-years). Thirty cases of leukaemia (25 dead and 5 alive) were detected in the former and four cases (all dead) in the latter. The leukaemia mortality rate was 14/100,000 person-years in the benzene cohort and 2/100,000 person-years in the control cohort; the standardized mortality ratio was 5.74 (p less than 0.01 by U test). The average latency of benzene leukaemia was 11.4 years. Most (76.6%) cases of benzene leukaemia were of the acute type. The mortality due to benzene leukaemia was high in organic synthesis plants followed by painting and rubber synthesis industries. The concentration of benzene to which patients with a leukaemia were exposed ranged from 10 to 1000 mg/m3 (mostly from 50 to 500 mg/m3). Of the 25 cases of leukaemia, seven had a history of chronic benzene poisoning before the leukaemia developed.

Adult↗
PubMed1986

Possible ethnic difference in toluene metabolism: a comparative study among Chinese, Turkish and Japanese solvent workers.

Toluene metabolism was studied in 192 Chinese workers in comparison with that in 130 Japanese and 17 Turks. Time-weighted average concentrations of toluene in the breathing zone of workers were measured utilizing passive dosimeters, and hippuric acid (HA) and omicron-cresol (omicron C) concentrations in shift-end spot urine samples by high-performance liquid chromatography (HPLC) and gas chromatography (GC), respectively. Under similar exposure conditions, male Japanese excreted almost twice as much HA as male Chinese, although such difference was less marked between female Chinese and Japanese. In contrast, the excretion of oC did not differ between the two ethnic groups. The ratio of oC over HA was highest among Turkish workers followed by Chinese, and lowest among Japanese. Possible roles of differences in toxicogenetics as well as in life patterns were discussed.

China↗
PubMed1986

Benzene-specific increase in leukocyte alkaline phosphatase activity in rats exposed to vapors of various organic solvents.

Female Wistar rats were exposed to various solvent vapors 8 h/d for 7 d. The leukocyte suspension and serum were prepared from peripheral blood and utilized for the determination of alkaline phosphatase (AP) activity with disodium phenyl phosphate as a substrate [leukocyte AP (LAP) and serum AP (SAP) assay]. While the exposure to benzene at 20 or 50 ppm did not cause significant changes in LAP activity, the exposure at 100 and 300 ppm resulted in a dose-dependent increase of LAP activity up to more than 100% over the control. No further increase was observed at 1000 or 3000 ppm. Similar exposure at 300 ppm to either toluene, m-xylene, n-hexane, trichloroethylene, methyl ethyl ketone, ethyl acetate, or methyl alcohol did not induce any changes in LAP activity. Thus, the increase in LAP activity was considered to be specific to benzene exposure. When the animals were exposed to toluene (300 ppm) in combination with benzene (300 ppm), not only was the benzene-induced leukopenia alleviated as previously reported, but the benzene-induced increase in LAP activity was no longer observed. The parallel inhibitory effects of toluene on benzene-induced increase in LAP and leukopenia suggest that a relation may exist between increase in LAP activity and leukopenia. No changes in SAP activities were observed in the rats under the exposure conditions examined.

Alkaline Phosphatase↗
PubMed1986

Quantitative relation of urinary phenol levels to breathzone benzene concentrations: a factory survey.

Urine samples were collected from 64 men and 88 women in shoe factories and printing plants at the end of a seven hour day shift in the latter half of a week in spring. Urine samples were also taken from 43 men and 88 women in the same factories but who were not exposed to solvents. Exposure to benzene during the shift was monitored by passive dosimeters. Both phenol in urine and benzene in activated carbon were analysed with FID gas chromatographs. The urinary concentrations of phenol were linearly related to the time weighted average concentrations of benzene in the breathzone air; the variation was so small that those exposed to 10 ppm benzene could be separated from the non-exposed at least on a group basis when the phenol concentration was corrected either for creatinine concentration or for specific gravity. The urinary phenol concentrations corresponding to 10 ppm benzene were 47.5 mg/l (as observed), 57.9 mg/g creatinine, or 46.6 mg/l (specific gravity 1.016).

Adult↗