Abstract
Female BDF1 mice were exposed to 100, 300 and 900 ppm benzene 6 h/day, 5 days/week, up to 8 weeks. Hematological studies included peripheral blood data, T4 and T8 lymphocyte counts in the blood and the spleen, hemopoietic stem and progenitor cell assays in the marrow (CFU-S, CFU-C, BFU-E, CFU-E). The single cell gel assay (“comet assay”) was applied in parallel with cells from the peripheral blood, bone marrow, spleen and liver. The results showed minor changes in the stem and progenitor cells and the development of a slight anemia at 4 and 8 weeks, in agreement with reported data. New was the increase of the T4/T8 ratio in the peripheral blood (not in the spleen) at the end of the first week of exposure to 300 and 900 ppm. The results of the “comet assay” indicate a much higher sensitivity of this test system (strand breaks and alkali labile sites of DNA). The tail moment indicative of the damage to DNA increased as early as 3 days with 300 ppm in the peripheral blood cells. Furthermore, the liver cells did react to a much higher extent than the other cells tested. With 100 ppm significant changes were seen in the liver after 5 days, but not in the blood. The repair, studied 24 and 48 h after the end of the exposure, was almost complete after 5-day exposure period in the blood and the liver, but not after 4 weeks of exposure with 300 ppm in the blood, and 100 and 300 ppm in the liver.
Similar content being viewed by others
References
Aksoy M (1989) Benzene carcinogenicity. CRC Press, Boca Raton
Au WW, Ramanujam VMS, Ward JB Jr, Legator MS (1991) Chromosome aberrations in lymphocytes of mice after sub-acute low-level inhalation exposure to benzene. Mutat Res 260: 219–224
Baarson KA, Snyder CA, Albert RE (1984) Repeated exposure of C57B1 mice to inhaled benzene at 10 ppm markedly depressed erythropoietic colony formation. Toxicol Lett 20: 337–342
Cronkite EP (1986) Benzene hematotoxicity and leukemogenesis. Blood Cells 12: 129–137
Erexson GL, Wilmer JL, Steinhagen WH, Kligerman AD (1986) Induction of cytogenetic damage in rodents after short-term inhalation of benzene. Environ Mutagen 8: 29–40
Frankenberg-Schwager M (1990) Induction, repair and biological relevance of radiation-induced DNA lesions in eukaryotic cells. Radiat Environ Biophys 29: 273–292
Gad-El Karim MM, Ramanujam VMS, Legator MS (1986) Correlation between the induction of micronuclei in bone marrow by benzene exposure and the excretion of metabolites in urine of CD-1 mice. Toxicol Appl Pharmacol 85: 464–477
Hilderbrand RL, Murphy MJ Jr (1983) The effects of benzene inhalation on murine hematopoietic precursor cells (CFU-E, CFU-GM). Int J Cell Cloning 1: 240
Necas E, Barthel E, Seidel HJ (1992) Sensitivity of CFU-E to exogenous erythropoietin in benzene treated mice. Ann Hematol 64: 12–15
Olive PL, Banath JP, Durand RE (1990) Heterogeneity in radiation-induced DNA damage and repair in tumour and normal cells measured using the “Comet” assay. Radiat Res 122: 86–94
Rozen MG, Snyder CA, Albert RE (1984) Depression in B- and T-lymphocyte mitogen-induced blastogenesis in mice exposed to low concentrations of benzene. Toxicol Lett 20: 343–349
Schad H, Schäfer F, Weber L, Seidel HJ (1992) Determination of benzene metabolites with solid phase extraction and HPLC in urine of mice. J Chromatogr 593: 147–151
Seidel HJ, Barthel E, Zinser D (1989a) The hematopoietic stem cell compartment in mice during and after longterm inhalation of three doses of benzene. Exp Hematol 17: 300–303
Seidel HJ, Beyvers G, Pape M, Barthel E (1989b) The influence of benzene on the erythroid cell system in mice. Exp Hematol 17: 760–764
Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175: 184–191
Tice RR, Costa DL, Drew RT (1980). Cytogenetic effects of inhaled benzene in murine bone marrow: induction of sister chromatide exchanges, chromosomal aberrations, and cellular proliferation inhibition in DBA/2 mice. Proc Natl Acad Sci USA 77: 2148–2152
Tice RR, Vogt TF, Costa DL (1981) Effects of sex, strain, age, and route of exposure on benzene-induced sister chromatide exchange (SCE) in murine bone marrow. Environ Mutagen 3: 338–339
Tice RR, Sawey MJ, Drew RT, Cronkite EP (1984) Benzene-induced micronuclei in the peripheral blood of mice. A retrospective analysis. Environ Mutagen 6: 421
Tice RR, Andrews PW, Singh NP (1990) The single cell gel assay. A sensitive technique for evaluating intercellular differences in DNA damage and repair. In: Sutherland BM, Wordhead AD (eds) DNA damage and repair in human tissues. Plenum, NY, pp 291–301
Vacha J, Znojil V, Seidel HJ, Barthel E (1990) Ferrokinetics and erythropoiesis in mice after longterm inhalation of benzene. Blut 60: 41–47
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Plappert, U., Barthel, E., Raddatz, K. et al. Early effects of benzene exposure in mice. Hematological versus genotoxic effects. Arch Toxicol 68, 284–290 (1994). https://doi.org/10.1007/s002040050070
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s002040050070