Sister chromatid exchange in regenerating liver and bone marrow cells of mice exposed to styrene

doi:10.1016/0041-008X(79)90163-7

Toxicology and Applied Pharmacology

Volume 50, Issue 2, 15 September 1979, Pages 365-367

https://doi.org/10.1016/0041-008X(79)90163-7 Get rights and content

Abstract

Following exposure of BDF₁ males to 565 ± 15.8 ppm styrene for 4 days (6 hr/day), sister chromatid exchange frequencies were analyzed simultaneously in regenerating liver and bone marrow cells from exposed mice. Comparisons were made with nonexposed controls. Regenerating liver as well as bone marrow cells showed a three-to four fold increase relative to the control.

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W.K. de Raat
Induction of sister chromatid exchanges by styrene and its presumed metabolite styrene oxide in the presence of rat liver homogenate
Chem.-Biol. Interact.
(1978)
H. Kato
Spontaneous and induced sister chromatid exchanges as revealed by the BrdU labeling method
Int. Rev. Cytol.
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The metabolism of styrene in the rat and the stimulatory effect of phenobarbital
Toxicol. Appl. Pharmacol.
(1971)
E.L. Schneider et al.
Bromodeoxyuridine differential chromatid staining technique: A new approach to examining sister chromatid exchange and cell replication kinetics
J.W. Allen et al.
In vivo BrdU-33258 Hoechst analysis of DNA replication kinetics and sister chromatid exchange formation in mouse somatic and meiotic cells
Chromosoma
(1976)

There are more references available in the full text version of this article.

Cited by (21)

Review of the in vivo genotoxicity tests performed with styrene
2005, Mutation Research - Reviews in Mutation Research
Results from new genotoxicity tests in laboratory animals have necessitated a comprehensive re-evaluation of the mutagenic potential of styrene in vivo. Available data suggest that styrene, after being metabolized to styrene oxide, is weakly positive in indicator tests detecting DNA adducts, DNA strand breaks and sister chromatid exchanges (SCEs). There is no convincing evidence of styrene clastogenicity in experimental animals when the quality of the studies and the plausibility of the test results are considered. Equivocal results were obtained after exposure to high doses causing lethality. A recently published in vivo micronucleus test (MNT) in bone marrow cells of mice conforming to the current OECD guideline was clearly negative. Consequently, our evaluation of the published genotoxicity data comes to the conclusion that styrene at high doses can induce genotoxic effects in indicator tests. These DNA effects depend upon the exposure levels of the target cells, the metabolic activation to styrene oxide and the efficiency of detoxification. Mutagenic effects of styrene can only be expected under extreme exposure conditions if styrene oxide is not efficiently detoxified and primary DNA lesions are not completely repaired. However, there is no clear evidence that styrene induces mutagenic/clastogenic effects in vivo when tested under appropriate test conditions.
A re-evaluation of the cytogenetic effects of styrene
1994, Mutation Research/Reviews in Genetic Toxicology
Results from new chromosome studies in laboratory animals, comparative investigations of styrene metabolism and pharmacokinetics in humans and animals, and several recent cytogenetic surveys of styrene-exposed workers have necessitated a comprehensive re-evaluation of the chromosome-damaging effects of this chemical.
Both styrene and its genotoxic metabolite, styrene oxide, can induce chromosome aberrations (CA) and sister chromatid exchanges (SCE) in vitro, but the chromosome-damaging ability of styrene is only manifested if test conditions favour its metabolic activation over inactivation.
There is no convincing evidence of styrene clastogenicity in experimental animals. Styrene oxide is clastogenic only at lethal concentrations via i.p. injection in Chinese hamsters (but not via inhalation) or after oral treatment of mice, a route considered inappropriate for investigating the chromosome-damaging potential of inhaled styrene in man. Styrene and styrene oxide can induce SCE in animals at very high concentrations.
Eighteen of 52 cytogenetic studies (CA, micronuclei, SCE) on peripheral blood lymphocytes of styrene workers have reported increases in chromosome damage. The positive findings are not compatible with the conclusion that styrene is responsible for the cytogenetic effects for the following reasons.
- 1.
  (a) The positive or negative outcome of the various investigations bears no relationship to the degree of exposure of the workers.
- 2.
  (b) There is no convincing evidence of a positive dose response relationship.
- 3.
  (c) The relative induction of CA and SCE in worker studies are the opposite of observations of styrene effects in cultured lymphocytes and in laboratory animals.
- 4.
  (d) The reports of chromosome-type exchanges in some studies of styrene workers is inconsistent with observations of styrene clastogenicity in cultured lymphocytes.
- 5.
  (e) Reports of SCE induction in workers exposed to low concentrations of styrene are not compatible with results of animal inhalation studies, particularly in view of the differences in styrene metabolism and pharmacokinetics between humans and rodents.
The increases in cytogenetic effects reported in some studies on styrene workers are probably attributable to the presence of other chromosome-damaging agents in the workplace and/or to inadequate investigations.
Sister-chromatid exchange: second report of the Gene-Tox program
1993, Mutation Research/Reviews in Genetic Toxicology
This paper reviews the ability of a number of chemicals to induce sister-chromatid exchanges (SCEs). The SCE data for animal cells in vivo and in vitro, and human cells in vitro are presented in 6 tables according to their relative effectiveness. A seventh table summarizes what is known about the effects of specific chemicals on SCEs for humans exposed in vivo. The data support the concept that SCEs provide a useful indication of exposure, although the mechanism and biological significance of SCE formation still remain to be elucidated.
Cytogenetic studies of mice exposed to styrene by inhalation
1992, Mutation Research/Genetic Toxicology
The data for the in vivo genotoxicity of styrene (STY) are equivocal. To evaluate the clastogenicity and sister-chromatid exchange (SCE)-inducing potential of STY in vivo under carefully controlled conditions, B₆C₃F₁ female mice were exposed by inhalation for 6 h/day for 14 consecutive days to either 0, 125, 250 or 500 ppm STY. One day after the final exposure, peripheral blood, spleen, and lungs were removed and cells were cultured for the analysis of micronucleus (MN) induction using the cytochalasin B-block method, chromosome breakage, and SCE induction. Peripheral blood smears were also made for scoring MN in erythrocytes. There was a significant concentration-related elevation of SCE frequency in lymphocytes from the spleen and the peripheral blood as well as in cells from the lung. However, no statistically significant concentration-related increases were found in the frequency of chromosome aberrations in the cultured splenocytes or lung cells, and no significant increases in MN frequencies were observed in binucleated splenocytes or normochromatic erythrocytes in peripheral blood smears.
Species differences in the genotoxicity of cyclophosphamide and styrene in three in vivo assays
1992, Mutation Research/Environmental Mutagenesis and Related Subjects
Species differences in dispositional factors such as distribution, metabolism and excretion may often account for species differences in the toxic responses to foreign chemicals. In this study we compared the genotoxic responses of cyclophosphamide (CP) and styrene (ST) between Porton rats and LACA Swiss mice in three in vivo assays (bone marrow micronucleus (MN), sperm morphology (SM) and sister-chromatid exchange (SCE) assays). The sensitivities of the three assays were compared by the doses of the compounds required to elicit a significant genotoxic response. The baseline levels for the MN, SCE and SM assays were 1.1–1.4 and 1.2–1.3 MNPCEs/1000 PCEs, 0.23–0.24 and 0.20–0.21 SCEs/chromosome, 3.5–5.7% and 1.6–1.9% abnormal sperm in mice and rats, respectively. CP was a potent genotoxin in the MN and SCE assays but weakly genotoxic in the SM assay. At comparable doses, the rat was approximately 3-, 2.5- and 1.8-fold more sensitive to CP than mice in the MN, SM and SCE assays, respectively. ST produced weak genotoxic responses in all assays in mice and only in the SM and SCE assays in rats. The mice were more sensitive to ST in the MN and SM assays, while it was difficult to compare the species in the SCE assay. For both compounds the sensitivity of the three assays, in decreasing order, were SCE>MN⪢SM. For CP the relative responses in the Porton rats and LACA Swiss mice were qualitatively similar to previous reports. Although the use of different strains may explain differences between the studies in the magnitude of the responses observed. The results for ST in the rat shows that the choice of genotoxic endpoint can determine whether a response is detectable. Moreover, the discrepancies between the results for ST in this study and others, suggest that as well as using a battery of in vivo tests, it may be prudent to select more that one strain or species to fully assess a compound's ability to produce DNA damage.
The genetic toxicology of styrene and styrene oxide
1991, Mutation Research/Reviews in Genetic Toxicology

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Toxicology and Applied Pharmacology

Abstract

References (10)

Induction of sister chromatid exchanges by styrene and its presumed metabolite styrene oxide in the presence of rat liver homogenate

Chem.-Biol. Interact.

Spontaneous and induced sister chromatid exchanges as revealed by the BrdU labeling method

Int. Rev. Cytol.

The metabolism of styrene in the rat and the stimulatory effect of phenobarbital

Toxicol. Appl. Pharmacol.

Bromodeoxyuridine differential chromatid staining technique: A new approach to examining sister chromatid exchange and cell replication kinetics

In vivo BrdU-33258 Hoechst analysis of DNA replication kinetics and sister chromatid exchange formation in mouse somatic and meiotic cells

Chromosoma

Cited by (21)

Review of the in vivo genotoxicity tests performed with styrene

A re-evaluation of the cytogenetic effects of styrene

Sister-chromatid exchange: second report of the Gene-Tox program

Cytogenetic studies of mice exposed to styrene by inhalation

Species differences in the genotoxicity of cyclophosphamide and styrene in three in vivo assays

The genetic toxicology of styrene and styrene oxide

Short communicationSister chromatid exchange in regenerating liver and bone marrow cells of mice exposed to styrene

Abstract

Chem.-Biol. Interact.

Int. Rev. Cytol.

Toxicol. Appl. Pharmacol.

In vivo BrdU-33258 Hoechst analysis of DNA replication kinetics and sister chromatid exchange formation in mouse somatic and meiotic cells

Chromosoma

Short communication
Sister chromatid exchange in regenerating liver and bone marrow cells of mice exposed to styrene