US EPA

2753835 

Journal Article 

DOSE-RELATED CLASTOGENIC EFFECTS INDUCED BY BENZENE IN BONE MARROW CELLS AND IN DIFFERENTIATING SPERMATOGONIA OF SWISS CD1 MICE 

Ciranni, R; Barale, R; Adler, ID 

1992 

1 

Mutation Research Letters
ISSN: 0165-7992 

EMIC/87163 

271 

2 

English 

TO ANSWER THE QUESTION WHETHER A GENOTOXIC CARCINOGEN MIGHT BE A GERM-CELL MUTAGEN, CYTOGENETIC DAMAGE INDUCED BY BENZENE WAS EVALUATED IN BOTH BONE MARROW CELLS (BM) AND DIFFERENTIATING SPERMATOGONIA (SPG) OF MALE SWISS CD1 MICE. THE ANALYSIS WAS PERFORMED BY DETERMINING THE FREQUENCIES OF CHROMOSOMAL ABERRATIONS IN BOTH CELL TYPES AFTER 1 ML/KG OF SINGLE BENZENE PER OS ADMINISTRATION. A WIDE RANGE OF TIMES (6, 12, 18, 24, 30, 36, 42, 48 H) WAS TESTED TO DETERMINE THE TIME OF MAXIMUM RESPONSE. THE PEAK OF MAXIMUM CLASTOGENIC EFFECT WAS FOUND 24 H AFTER TREATMENT BOTH IN BM CELLS AND IN SPG. THE CLASTOGENIC EFFECT WAS HIGHER (3-FOLD) IN BM THAN IN SPG CELLS. TWO ADDITIONAL DOSES (0.1 AND 0.5 ML/KG FOR BM; 0.25 AND 0.5 ML/KG FOR SPG) WERE TESTED TO DETERMINE THE DOSE-RESPONSE RELATIONSHIP. THE INCREASE IN ABERRANT CELLS WAS LINEAR-QUADRATIC IN BM AND LINEAR IN SPG. A QUANTITATIVE COMPARISON WAS PERFORMED BY CALCULATING THE DOUBLING DOSE (DD) FOR BOTH CELL TYPES. THE DD IS DEFINED AS THE DOSE THAT INDUCED AS MANY ABERRANT CELLS AS OCCUR SPONTANEOUSLY PER CELL GENERATION. FOR BM ONLY THE DATA FOR THE LOWER TWO DOSES WERE INCLUDED BECAUSE AT THE HIGHER DOSE THE CURVE DEVIATED FROM LINEARITY. THE DD WERE 0.25 ML/KG FOR BM AND 0.33 ML/KG FOR SPG. WE MAY REASONABLY CONCLUDE THAT BZ IS A GERM-CELL CLASTOGEN.