Modifications in the metabolism and myeloclastogenic effect of benzene
Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase analysis. In a series of experiments, male and female CD-1 mice were subjected to various pretreatments: phenobarbital (PB) (0.1% in drinking water x 7 days or 80 mg/kg/day (I.P.) x 3 days before treatment), 3-methylcholanthrene (3-MCA) (30 mg/kg/day (I.P.) x 2 days), SKF-525A (80 mg/kg (I.P.) 2 hours before each treatment dose), or Aroclor-1254 (100 mg/kg) (I.P.) once, 5 days before treatment. The animals were then treated with benzene (440 or 880 mg/kg) or toluene (860 or 1720 mg/kg) or their mixture in 2 doses 24 hours apart and sacrificed 6 hours or 24 hours after the second dose. Toluene showed no clastogenic activity and reduced the clastogenic effect of benzene when the mixture was given. None of the pretreatments protected against the clastogenic effect of benzene. 3-MCA pretreatment caused a tremendous enhancement of benzene myeloclastogenicity. The sex difference, with females constantly more resistant than males to benzene, was retained among the 3-MCA pretreated group. Toluene, in mixture with benzene, lowered the clastogenic effect in 3-MCA pretreated mice. Dose-response curves with benzene treatment alone and with 3-MCA induced groups were generated in which the former curve was lower for each dose than the latter. Urine fractions were collected at 12-hour intervals from 3-groups of 10 males gavaged with benzene, either non-induced, PB- or 3MCA induced. Catechol was the major metabolite, phenol the minor one, and hydroquinone and semiquinones were present in trace amounts.
- Research Organization:
- Univ. of Texas Medical Branch, Galveston
- OSTI ID:
- 5762115
- Journal Information:
- Environmental Mutagen Society; (United States), Journal Name: Environmental Mutagen Society; (United States)
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BENZENE
BIOLOGICAL EFFECTS
METABOLISM
TOLUENE
3-METHYLCHOLANTHRENE
BONE MARROW
DOSE-RESPONSE RELATIONSHIPS
METABOLITES
MICE
PHENOBARBITAL
PHENOL
PYROCATECHOL
QUINONES
SEX DEPENDENCE
SYNERGISM
ALKYLATED AROMATICS
ANESTHETICS
ANIMAL TISSUES
ANIMALS
ANTICONVULSANTS
AROMATICS
AZINES
BARBITURATES
BODY
CENTRAL NERVOUS SYSTEM DEPRESSANTS
DEVELOPERS
DRUGS
HEMATOPOIETIC SYSTEM
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
HYPNOTICS AND SEDATIVES
MAMMALS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PHENOLS
POLYCYCLIC AROMATIC HYDROCARBONS
POLYPHENOLS
PYRIMIDINES
RODENTS
TISSUES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)