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

Jonathan B. Ward, Marinel M. Ammenheuser, V-M Ramanujam, Debra L. Morris, Elbert B. Whorton, Marvin S. Legator

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 autoradiogaaphic 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 recoverd 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 × 10-6 at 0 ppb; 29.2 × 10-6 at 40 ppb; 62.5 × 10-6 at 100 ppb and 25.0 × 10-6 at 1000 ppb. The Vf of unexposed mice housed in standard cages was 13.2 × 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 < 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.

Original languageEnglish (US)
Pages (from-to)49-57
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume268
Issue number1
DOIs
StatePublished - 1992
Externally publishedYes

Fingerprint

Inhalation Exposure
Benzene
Lymphocytes
Spleen
Mutation
United States Occupational Safety and Health Administration
Thioguanine
Hypoxanthine
Guanine
Transferases
Thymidine
Inhalation
Plastics
Chromosomes
Air

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis

Cite this

The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice. / Ward, Jonathan B.; Ammenheuser, Marinel M.; Ramanujam, V-M; Morris, Debra L.; Whorton, Elbert B.; Legator, Marvin S.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 268, No. 1, 1992, p. 49-57.

Research output: Contribution to journalArticle

Ward, Jonathan B. ; Ammenheuser, Marinel M. ; Ramanujam, V-M ; Morris, Debra L. ; Whorton, Elbert B. ; Legator, Marvin S. / The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 1992 ; Vol. 268, No. 1. pp. 49-57.
@article{a1c870e0572043499255de8798d4d928,
title = "The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice",
abstract = "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 autoradiogaaphic 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 recoverd 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 × 10-6 at 0 ppb; 29.2 × 10-6 at 40 ppb; 62.5 × 10-6 at 100 ppb and 25.0 × 10-6 at 1000 ppb. The Vf of unexposed mice housed in standard cages was 13.2 × 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 < 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.",
author = "Ward, {Jonathan B.} and Ammenheuser, {Marinel M.} and V-M Ramanujam and Morris, {Debra L.} and Whorton, {Elbert B.} and Legator, {Marvin S.}",
year = "1992",
doi = "10.1016/0027-5107(92)90082-D",
language = "English (US)",
volume = "268",
pages = "49--57",
journal = "Mutation Research",
issn = "0027-5107",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice

AU - Ward, Jonathan B.

AU - Ammenheuser, Marinel M.

AU - Ramanujam, V-M

AU - Morris, Debra L.

AU - Whorton, Elbert B.

AU - Legator, Marvin S.

PY - 1992

Y1 - 1992

N2 - 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 autoradiogaaphic 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 recoverd 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 × 10-6 at 0 ppb; 29.2 × 10-6 at 40 ppb; 62.5 × 10-6 at 100 ppb and 25.0 × 10-6 at 1000 ppb. The Vf of unexposed mice housed in standard cages was 13.2 × 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 < 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.

AB - 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 autoradiogaaphic 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 recoverd 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 × 10-6 at 0 ppb; 29.2 × 10-6 at 40 ppb; 62.5 × 10-6 at 100 ppb and 25.0 × 10-6 at 1000 ppb. The Vf of unexposed mice housed in standard cages was 13.2 × 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 < 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.

UR - http://www.scopus.com/inward/record.url?scp=0026645019&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026645019&partnerID=8YFLogxK

U2 - 10.1016/0027-5107(92)90082-D

DO - 10.1016/0027-5107(92)90082-D

M3 - Article

VL - 268

SP - 49

EP - 57

JO - Mutation Research

JF - Mutation Research

SN - 0027-5107

IS - 1

ER -