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Biomedical subjects

J B Ward

Publications and source records attributed to J B Ward.

At least 37 records · Page 2Linked to original sources
PubMed1995

The use of propofol and mivacurium anesthetic technique for the immediate postoperative adjustment of sutures in strabismus surgery.

PURPOSE: Adjustable suture techniques have become increasingly popular over the last decade and may reduce the re-operation rate after strabismus surgery. The adjustment usually is made in the hospital or office 5 to 24 hours after surgery, when the patient has fully recovered from general anesthesia. The ability to perform suture adjustment in the operating room, immediately after completion of surgery, would be an attractive alternative with respect to patient monitoring, sterility, comfort, and timing. The purpose of this study is to compare the alignment of patients in the operating room adjusted immediately after surgery with their alignment the morning after surgery. METHODS: Patients with strabismus who have good vision in each eye and who were judged to be appropriate candidates for adjustable sutures were invited to enroll in a study using propofol and mivacurium total intravenous anesthetic technique. Patients underwent strabismus surgery in which one or more muscles were placed on adjustable sutures. Immediately after extubation, these patients were awakened in the operating room, assisted in sitting upright, and asked to fixate on a 20/400 Snellen E target on the operating room wall. Sutures were adjusted, when necessary, to obtain the desired postoperative alignment. Prism and alternate cover measurements, taken after the sutures were permanently tied, were compared with measurements taken the morning after surgery. RESULTS: Twenty-nine patients qualified for inclusion. Measurements of horizontal and vertical alignment in the operating room were all within 12 prism diopters (PD) of the measurements taken 18 to 24 hours after surgery (mean variation, 4 PD horizontally and 2 PD diopters vertically). The measured deviation changed less than or equal to 6 PD horizontally in 78% of patients and less than or equal to 3 PD vertically in 70% of patients. CONCLUSION: For some adult patients with strabismus, a total intravenous general anesthesia technique using an infusion of propofol and mivacurium may provide the opportunity for accurate suture adjustment in the operating room, immediately after completion of surgery.

Adolescent↗
PubMed1994

Elevated frequencies of hprt mutant lymphocytes in cigarette-smoking mothers and their newborns.

Maternal cigarette smoking during pregnancy has been associated with increased perinatal mortality and low birth weight. Several epidemiological studies have demonstrated an association between smoking during pregnancy and an elevated risk of hematopoietic cancer in the child, but other studies have failed to confirm this association. We have used an assay for somatic cell mutation to evaluate the in utero effects of exposure to maternal cigarette smoking. Cord blood samples were obtained from 10 newborns whose mothers smoked cigarettes during pregnancy and 10 newborns of non-smoking mothers. Blood samples were also obtained from 5 of the smoking and 5 of the non-smoking mothers. Smoking status was confirmed in all samples by testing the blood plasma for cotinine. The frequency of lymphocytes containing mutations at the hypoxanthine phosphoribosyltransferase (hprt) locus was determined with an autoradiographic assay using cells that had been cryopreserved. The mothers who were smokers had a mean frequency (+/- SE) of 3.08 (+/- 0.55) variant (mutant) cells per 10(6) evaluatable lymphocytes. The frequency (Vf) in non-smokers was 1.07 (+/- 0.17) x 10(-6). The Vf of newborns of smokers was 2.17 (+/- 0.24) x 10(-6), and newborns of non-smokers had a Vf of 0.77 (+/- 0.13) x 10(-6). In both mothers and newborns the difference in Vf between smokers and non-smokers was statistically significant (p < 0.05). Maternal and newborn Vfs were significantly correlated (r = 0.88; p < 0.004), and there was a positive association (r = 0.86; p < 0.001) between the reported number of cigarettes smoked per day and the Vfs. This study provides further evidence that maternal smoking may be hazardous to the future health of children exposed in utero to mutagenic agents in cigarette smoke.

Adult↗
PubMed1994

Species differences in urinary butadiene metabolites: comparisons of metabolite ratios between mice, rats, and humans.

We have previously identified two metabolites, 1,2-dihydroxy-4-(N-acetylcysteinyl-S-)-butane (M-I) and 1-hydroxy-2-(N-acetylcysteinyl-S-)-3-butene (M-II) in the urine of mice, rats, hamsters, and monkeys exposed by inhalation to 8000 ppm [14C]butadiene. The sum of these two metabolites constituted between 50 and 90% of the total urinary [14C]butadiene equivalents. When comparing species, the ratios of excreted M-I relative to the total of M-I + M-II were linearly related to hepatic epoxide hydrolase activities, with mice displaying the lowest ratios and monkeys displaying the highest ratios. Because humans are known to have epoxide hydrolase activities more similar to those of monkeys than mice, we postulated that after inhalation of butadiene, humans would excrete predominantly M-I and little M-II. To address this hypothesis, we measured the two metabolites in the urine of workers occupationally exposed to butadiene. We initially developed an assay to measure the two metabolites in urine using techniques not dependent on radiolabeled compounds. The assay is based on isotope-dilution gas chromatography/mass spectroscopy. After addition of deuterated internal standards, the metabolites were isolated from urine samples by solid-phase extraction and selective precipitation. The metabolites were converted to volatile derivatives by trimethylsilylation prior to analysis. The assay is sensitive down to at least 100 ng/ml of both metabolites in urine. The assay was applied to urine samples of humans occupationally exposed to butadiene in a production plant. M-I, but not M-II, could be readily identified and quantitated in the urine samples at levels frequently greater than 1 microgram/ml, thus supporting our hypothesis. Employees who worked in production areas with historical atmospheric concentrations of 3-4 ppm butadiene could be distinguished as a group from those outside controls. Finally, mice and rats were exposed to 11.7 ppm butadiene for 4 hr, and the ratio of the two metabolites was measured. For mice, the ratios of M-I to M-I + M-II were similar to those reported previously following exposure to 8000 ppm. In contrast, for rats, M-I represented a higher proportion of the excreted metabolites at the lower exposure level. These results confirm earlier in vitro studies that suggested the predominant pathway for clearance of BDO in humans is by hydrolysis rather than direct conjugation with glutathione.

Acetylcysteine↗
PubMed1994

hprt mutant lymphocyte frequencies in workers at a 1,3-butadiene production plant.

1,3-Butadiene is a major industrial chemical that has been shown to be a carcinogen at multiple sites in mice and rats at concentrations as low as 6.25 ppm. Occupational exposures have been reduced in response to these findings, but it may not be possible to determine by using traditional epidemiological methods, whether current exposure levels are adequate for protection of worker health. However, it is possible to evaluate the biological significance of exposure to genotoxic chemicals at the time of exposure by measuring levels of genetic damage in exposed populations. We have conducted a pilot study to evaluate the effects of butadiene exposure on the frequencies of lymphocytes containing mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in workers in a butadiene production plant. At the same time, urine specimens from the same individuals were collected and evaluated for the presence of butadiene-specific metabolites. Eight workers from areas of the plant where the highest exposures to butadiene occur were compared to five workers from plant areas where butadiene exposures were low. In addition, six subjects with no occupational exposure to butadiene were also studied as outside controls. All of the subjects were nonsmokers. An air sampling survey conducted for 6 months, and ending about 3 months before the study, indicated that average butadiene levels in the air of the high-exposure areas were about 3.5 +/- 7.5 ppm. They were 0.03 +/- 0.03 ppm in the low-exposure areas. Peripheral blood lymphocytes from the subjects were assayed using an autoradiographic test for hprt mutations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Site-directed mutagenesis of the photosystem I reaction center in chloroplasts. The proline-cysteine motif.

Site-directed mutagenesis has been used to introduce specific amino acid changes into the photosystem I reaction center in the green alga Chlamydomonas reinhardtii. Plasmids containing mutated copies of the chloroplast psaB gene, encoding a polypeptide of the photosystem I reaction center heterodimer, were introduced into the chloroplast genome by particle bombardment. Successful transformants were selected by two procedures. The first involved complementation of a nonphotosynthetic mutant of Chlamydomonas, CC-2341 (ac-u-g-2.3), which has a frameshift mutation in the psaB gene, and selection of photosynthetic transformants on minimal medium. The second procedure utilized a co-transformation procedure with a plasmid containing a rRNA gene that confers spectinomycin resistance. Homologous replacement of the psaB gene was confirmed by screening for a unique restriction enzyme site within the transforming psaB sequences. These procedures have been used to specifically mutate a highly conserved proline-cysteine motif suggested to be important in coordinating the [4Fe-4S] iron-sulfur center Fx. Our results show that the cysteine is essential for assembly of the photosystem I reaction center although the adjacent proline fulfills no identifiable function. The approach described in this paper will be of value to future studies of the structure, function, and assembly of photosystem I.

Amino Acid Sequence↗
PubMed1993

A prospective, masked clinical trial of trifluridine, dexamethasone, and artificial tears in the treatment of epidemic keratoconjunctivitis.

Epidemics of viral conjunctivitis are a major public health problem in the Far East. No treatment has been shown to shorten the duration of illness. We studied the clinical course of epidemic keratoconjunctivitis in 74 patients during an outbreak of nearly 3,000 cases in late 1988 at a U.S. military base in the Philippines. Patients were randomly assigned to treatment with trifluridine, dexamethasone, or artificial tears, and examined in a double-masked fashion. There was no significant difference between the results of the three treatments. No bacterial cultures were positive. The prompt use of patient isolation, identification of nonadenoviral red eyes, and symptomatic treatment without steroids, antiviral, or antibiotic medication is recommended in cases of epidemic keratoconjunctivitis. This is the largest series of cases of epidemic keratoconjunctivitis with laboratory confirmation reported from the Philippines.

Adenovirus Infections, Human↗
PubMed1993

Use of haemoglobin adducts for biomonitoring exposure to 1,3-butadiene.

Measurement of specific adducts to haemoglobin can be used to establish the dosimetry of electrophilic compounds and metabolites in experimental animals and in man. Adducts of 1,2-epoxybutene with the N-terminal valine in haemoglobin were determined in male B6C3F1 mice and Sprague-Dawley rats following exposure by inhalation to low concentrations of 1,3-butadiene (0, 2, 10 or 100 ppm, 6 h/day, 5 days/week, 4 weeks; animals killed within 1 h after the last exposure). The adduct level increased linearly with butadiene concentration in the mice, whereas a deviation from linearity was observed in the rats. After exposure to 100 ppm butadiene, the adduct levels were four times higher in mice than in rats; at lower concentrations of butadiene, the species difference was less pronounced. Adduct levels of about 1-3 pmol/g globin were recorded in human subjects (nonsmokers) who worked in a production area where butadiene levels of about 1 ppm had been recorded in a survey conducted three to nine months prior to this study. Increased adduct levels were also observed in cigarette smokers (two subjects) who were not exposed occupationally to butadiene. Although preliminary, the data suggest that the adduct levels, and consequently the doses of epoxybutene per parts per million-hour of butadiene are lower in humans than in mice and rats. The adduct levels are much lower than those seen after occupational exposures to corresponding air levels of ethylene oxide and are lower than those seen after exposure to ethylene.

Adult↗
PubMed1993

Elevated somatic cell mutant frequencies and altered DNA repair responses in nonsmoking workers exposed to 1,3-butadiene.

Epidemiological evidence indicates that 1,3-butadiene is a human carcinogen; however, the epidemiological studies reflect past levels of exposures in the work place, which in all likelihood were higher than present-day levels. Studies of the metabolism of butadiene suggest that there may be qualitative differences among species in this respect. The question therefore arises as to the mutagenic and carcinogenic effects of butadiene in humans. The biomonitoring study reported here was designed to determine whether current exposure to this chemical in the work place is sufficient to induce mutations and/or to alter DNA repair functions, and to determine further whether levels of urinary metabolites correlate with the effects of exposure to butadiene. Nonsmoking workers in a butadiene production plant, who were exposed to levels of 1-3 ppm butadiene, were evaluated for hprt mutant frequencies, cytogenetic effects, including a challenge test to detect DNA repair deficiencies, and formation of protein adducts. We report here the results of the initial study on hprt mutant frequencies and of the challenge assay and the correlation between the results of these assays and levels of butadiene metabolite in the urine. A single metabolite of butadiene, 1,2-dihydroxy-4-(N-acetylcysteinyl-S)butane, was detected in the urine of all subjects. The concentration of the metabolite in the highly exposed group of workers was significantly higher than that in the group exposed to low concentrations or that in outside control groups. The correlation between the level of the metabolite in urine and the frequency of hprt mutants was r = 0.85 (p < 0.0003). Initial observations from a newly developed cytogenetic assay intended to measure altered DNA repair capability (the challenge assay) indicate a statistically significant increase in the high-exposure group relative to the low-exposure group (p < 0.01). This study thus reinforces and extends the results of the epidemiological studies and indicates that present exposure levels may not be sufficiently low to protect workers. It also provides evidence that levels of the urinary metabolite that was considered to be indicative of insensitivity correlate with the frequencies of somatic mutations and exposure to butadiene.

Butadienes↗
PubMed1992

Coumarin inhibits micronuclei formation induced by benzo(a)pyrene in male but not female ICR mice.

Coumarin has been shown to be an effective inhibitor of carcinogenesis in rodents if given before and during the carcinogen treatment. We investigated the possibility that pretreatment with coumarin would inhibit the genotoxicity of benzo(a)pyrene (BP) in ICR mice as indicated by the bone marrow micronucleus test, a widely used in vivo test for genotoxicity. Our studies showed that pretreatment of male mice with doses of coumarin at 65 or 130 mg/kg/day for 1 week (with 1 day of no treatment at midweek) partially inhibited the genotoxicity of BP at a single intraperitoneal dose of 150 mg/kg. Time course experiments showed a decrease in induced micronuclei in the bone marrow at several time points after the BP treatment, thus indicating a true inhibition and not a lag in the induction of micronuclei. However, no inhibition in micronuclei formation was seen in female mice pretreated with the same doses of coumarin. Coumarin treatment alone did not induce micronuclei in either sex. Future studies are needed to analyze the mechanisms responsible for the difference noted between the sexes.

Animals↗
PubMed1992

Cytogenetic analysis of pulmonary lavage and bone marrow cells of rats after repeated formaldehyde inhalation.

Cytogenetic analyses were conducted on bone marrow and pulmonary lavage cells from rats that received repeated inhalation exposures to formaldehyde. Male Sprague-Dawley rats were exposed to 0, 0.5, 3, or 15 ppm formaldehyde for 6 h per day, 5 days per week, for 1 and 8 weeks. There was no significant increase in chromosomal abnormalities in the bone marrow cells of formaldehyde-exposed rats relative to controls. There was a statistically significant increase in chromosomal aberrations in the pulmonary lavage cells from rats that inhaled 15 ppm. There were 7.6 and 9.2% of the scored pulmonary lavage cells that had aberrations following 1 and 8 weeks, respectively, of 15 ppm formaldehyde exposure (with control levels of 3.5 and 4.8%, respectively). The predominant damage seen was chromatid breaks. These findings indicate that marginal but statistically significant genotoxic effects could be detected locally in lung alveolar macrophages, but not distally in bone marrow, following repeated formaldehyde exposures only at a high concentration that is carcinogenic to rats. The biological significance of this effect is uncertain since formaldehyde is not considered to be a lung carcinogen in rats.

Administration, Inhalation↗
PubMed1992

The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice.

Benzene is a widely used chemical and common environmental contaminant. It is carcinogenic in man and animals and is genotoxic in mice, rats, and occupationally exposed humans at doses above one part per million. In order to evaluate the genotoxic effects of prolonged exposures to very low concentrations of benzene, we exposed CD-1 mice to benzene by inhalation for 22 h per day, seven days per week for six weeks at 40, 100 and 1000 parts per billion (ppb). Additional groups were exposed to purified air or were housed in standard plastic cages. The effects of in vivo exposure to benzene were evaluated by using an autoradiographic assay to determine the frequency of mutants which represent mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in spleen lymphocytes. At the end of the six weeks exposure period lymphocytes were recovered from the spleens of the mice and cryopreserved prior to assay. Mutant cells were selected on the basis of their ability to incorporate tritiated thymidine in the presence of 6-thioguanine. The weighted mean variant (mutant) frequencies (Vf) of female mice (three per group) were 7.2 x 10(-6) at 0 ppb; 29.2 x 10(-6) at 40 ppb; 62.5 x 10(-6) at 100 ppb and 25.0 x 10(-6) at 1000 ppb. The Vf of unexposed mice housed in standard cages was 13.2 x 10(-6). In male mice the same pattern of response was observed, but the increases in Vf in response to benzene were not as great. In both sexes of mice, the increases at 40 and 100 ppb were significantly greater than at 0 ppb (P less than 0.05). The increase in Vf with exposure to 100 ppb and the decline at 1000 ppb parallel the results observed for chromosome damage in spleen lymphocytes from the same animals (Au et al., Mutation Res., 260 (1991) 219-224). These results indicate that sub-chronic exposure to benzene at levels below the current Occupational Safety and Health Administration Permitted Exposure Limit may induce gene mutations in lymphocytes in mice.

Administration, Inhalation↗
PubMed1992

Incidence of sperm with two fluorescent bodies in men with impaired fertility.

OBJECTIVE: To determine the two fluorescent body (2FLB) frequency in males with impaired fertility. DESIGN: Males of couples were evaluated along with their female partners for reproductive function. They were classified as having the potential for fertility (control group) or as infertile (test group). This was based on the evaluation of both members of the couple. Semen parameters were determined and analyzed for differences among diagnostic groups. SETTING: The setting was clinical secondary care in both private and institutional practice. PATIENTS, PARTICIPANTS: The study population was composed of males of couples who were being evaluated for infertility. Classification as to reproductive potential and categories of abnormality was based on measurement of semen parameters and clinical judgment. INTERVENTIONS: Semen specimens were obtained and analyzed from 78 control and 93 test subjects. MAIN OUTCOME MEASURES: Semen parameters including volume, sperm count, sperm motility, percent morphologically abnormal sperm, and percent of quinacrine-stained sperm containing zero, one, or two FLBs were determined. RESULTS: The test group was found to have a 2FLB frequency that was significantly different from that of the control group. The data were then analyzed for significant differences in 2FLB frequencies in subpopulations. When subjects from all diagnostic subgroups that included varicocele were compared with the controls, the 2FLB frequency was significantly elevated (median percent of 2FLB was 1.2 versus 0.7). The 2FLB frequency in the remaining diagnostic groups was not elevated. CONCLUSIONS: This is the first report of an elevated 2FLB frequency associated with a biological abnormality. The cause of the elevated 2FLB frequency is not known. However, other anomalies that have been identified in varicocele patients have been associated with elevated intrascrotal temperatures. There are data available that associates elevated temperature with aneuploidy in mouse oocytes.

Humans↗
PubMed1992

Highly purified human alpha-thrombin promotes morphological transformation of BALB/c 3T3 cells.

Purified human alpha-thrombin stimulates phosphoinositide turnover as a necessary step in its stimulation of fibroblast cell proliferation. Since phosphoinositide turnover releases diacylglycerol, which activates protein kinase C, we postulated that long-term exposure to thrombin might promote cellular transformation in a manner similar to long-term exposure to phorbol esters, which also activate protein kinase C. The present studies show that chronic exposure of BALB/c 3T3 cells (subclone A31-1-13) to thrombin (5 micrograms/ml) led to a 4- to 20-fold increase in the frequency of morphological transformation over controls as determined by induced foci in monolayer cultures. The foci appeared to represent true transformants as cells from randomly selected foci grew in soft agar and had saturation densities 2- to 3-fold higher than control cells. Acute thrombin treatment for 24 h resulted in small but statistically significant (P less than 0.05) increases in morphological transformation with or without promotion by phorbol myristate acetate, indicating that thrombin can act as a weak initiator or complete carcinogen in this test system. Initiation of cells with low levels of 3-methylcholanthrene followed by promotion with thrombin caused a greater enhancement of morphological transformation (P less than 0.005). Thus, it appears that most of the stimulation of in vitro cell transformation by thrombin may be due to its promotional activity. These results raise the possibility that thrombin released locally following tissue injury or chronic irritation may play a role in cellular transformation and tumor development, especially in tissues sensitized by exposure to initiating carcinogens.

3T3 Cells↗
PubMed1991

Comparison of hprt variant frequencies and chromosome aberration frequencies in lymphocytes from radiotherapy and chemotherapy patients: a prospective study.

The autoradiographic 6-thioguanine-resistant mutant lymphocyte assay and a chromosome aberration assay were used to determine the time-course of appearance and persistence of elevated frequencies of hprt variants and dicentric chromosomes in patients receiving x-irradiation therapy. Twelve cancer patients, treated with 180-200 cGy/day, 5 days/wk, for 3-7 wk, were studied before treatment, at various weekly intervals during treatment, and after treatment. The hprt mutation assays were done with frozen/thawed lymphocytes isolated from aliquots of the same blood samples used for the chromosome aberration assays. The hprt variant frequencies (Vfs) of only 4 of the 7 patients assayed at 2 wk of treatment were elevated over pre-treatment Vfs, but during the 3rd and 4th weeks of treatment there were significant (P less than 0.01) 5- to 15-fold increases in all Vfs. By 6-32 wk after treatment Vfs had fallen to levels only slightly higher than the mean pre-treatment Vf. The frequencies of cells with dicentric chromosomes were significantly increased (P less than 0.01) after 1 wk of radiotherapy, continued to increase during therapy, and remained elevated after treatment. Five multiple sclerosis patients were also studied before and at 2 and 4 wk intervals after treatment with monthly i.v. doses of 750 mg/m2 of cyclophosphamide (CP). There were no significant elevations in chromosome aberrations at these post-treatment sample times. Previous assays for hprt mutants, done with aloquots of the same blood samples (Ammenheuser et al.: Mutat Res 204:509-520, 1988), had shown 8- to 20-fold increases in Vfs 2 wk after the 1st CP treatment. Our results demonstrate the complementary nature of these two human monitoring assays and emphasize the importance of careful selection of optimal sampling times.

Adult↗
PubMed1991

Factors contributing to chromosome damage in lymphocytes of cigarette smokers.

Cigarette smoking is generally believed to be responsible for a substantial number of human health problems. However, the causal relationship between smoking, the induction of biological effects and the extent of health problems among smokers have not been fully documented. Using the recently developed lymphocyte micronucleus (MN) assay, we have evaluated the chromosome aberration frequencies in 67 cigarette smokers and 59 matched non-smoking control subjects. We found that the mean MN frequency (per 100 cells) in the smokers was slightly higher than that found in the non-smokers (0.71 +/- 0.23 and 0.58 +/- 0.05 respectively; p less than 0.08). Factors which contribute to the expression of chromosome aberrations were also investigated. A significant age-dependent increase in MN frequencies was observed in both groups (p less than 0.05). Linear regression analysis showed that the age-dependent effects among smokers (r = 0.54; p less than 0.02) was further enhanced by cigarette consumption (r = 0.62; p less than 0.005). Consumption of low potency 'one-a-day' type multivitamins had no effect on MN frequencies in either sex of non-smokers and in the 1 male smoker who took multivitamins but vitamin intake consistently reduced the MN frequencies among female smokers. Using a challenge assay, fidelity of DNA repair was evaluated. Lymphocytes from both smokers and non-smokers were irradiated with single doses of 0 or 100 cGy of X-rays or with double doses of 100 cGy of X-rays each separated by 15 or 60 min (100/15 or 100/60). Chromosome translocation frequencies were consistently higher after irradiation in lymphocytes from smokers than in those from non-smokers. Statistically significant differences were detected when the cells were irradiated with the double doses of 100 cGy X-rays each separated by 60 min (p less than 0.05). These data suggest that lymphocytes from smokers made more mistakes in the repair of DNA damage than cells from non-smokers. Our studies provide new insights into the genotoxic effects of cigarette smoke and new information which may be useful for understanding the mechanisms for induction of health problems from smoking.

Aging↗
PubMed1991

Chromosome aberrations in lymphocytes of mice after sub-acute low-level inhalation exposure to benzene.

Male and female CD-1 mice were exposed to near ambient air concentrations of benzene by inhalation for 22 h per day, 7 days per week for 6 weeks. The concentrations were 0, 40, 100 and 1000 ppb. Significant increases in chromosome aberrations in spleen lymphocytes were observed in exposed compared with control mice except in the high-dose group (p less than 0.05 for female mice in 2 experiments and for male mice in 1 experiment; p less than 0.15 for male mice in the second experiment). A lack of increase in aberrations among mice of the high-dose group may be due to an induction of detoxifying enzymes as observed by us in a previous study (Au et al., 1988b). We also found that the female mice were more sensitive to the clastogenic activity of benzene than male mice under our experimental conditions. Our study serves to emphasize the need to conduct subchronic, low-dose in vivo genotoxicity studies using exposure conditions similar to those of humans, for evaluation of potential hazards. Our data suggest that the current occupational exposure concentrations for benzene (less than 1000 ppb) may still be hazardous to humans.

Administration, Inhalation↗