Bone marrow micronucleus assay: A review of the mouse stocks used and their published mean spontaneous micronucleus frequencies

Abstract

We have examined published negative control data from 581 papers on micronucleated bone marrow polychromatic erythrocytes (mnPCE) for differences in mean frequency and the frequency distribution profile among the mouse stocks used with the bone marrow micronucleus assay. For the 55 mouse stocks with published micronucleus assay data, the overall mean frequency is 1.95 mnPCE/1,000 PCE (1.95 mnPCE/1,000); for the 13 stocks most commonly used in the assay, it is 1.88 mnPCE/1,000. During the last 5 years, the mnPCE rate for these 13 major stocks has been 1.74 mnPCE/1,000. This current mean frequency is a substantial decrease from the mean of 3.07 mnPCE/1,000 observed for these 13 stocks for data published prior to 1981. Of the major stocks, the highest mean mnPCE negative control frequencies were observed for MS/Ae > BALB/c > C57Bl/6, and the lowest for CD-1 < Swiss Webster. We note that hybrid mouse stocks appear to have lower and less variable negative control frequencies than either of their parent strains and that the negative control frequency for some progeny stocks have diverged significantly from that of the parent stocks. Overall mean negative control frequencies appear to be correlated with breadth of the frequency distribution profile of published mean negative control values. Furthermore, a possible correlation between negative control frequency in the micronucleus assay and sensitivity to clastogens of different mouse strains may be indicated. The databases generated here allow us to define a range of norms for both the historical mean frequency and individual experimental mean frequencies for most stocks, but in particular, for the more commonly used mouse stocks. Our analysis, for the most part, bears out the recommendation of the first Gene-Tox Report on the micronucleus assay that the historical negative control frequency for a mouse stock should fall between 1 and 3 mnPCE/1,000. Eighty-six percent of the most commonly used mouse stocks have historical mean frequencies within this range. Though individual experimental mean values would not necessarily be expected to fall within the 1-3.00 mnPCE/1,000 range, 65.3% of the 2,327 published negative control values do, and 83.5% are < 3 mnPCE/1,000. The frequency with which an individual experimental mean value lies outside the 1.00 to 3.00 mnPCE/1,000 range differs among stocks and appears related to the mouse mean frequency. We suggest that the recommended range for historical mean frequency be extended slightly, to approximately 3.4 mnPCE/1,000, to accommodate some commonly used strains with overall mean negative control frequencies just above 3.00 mnPCE/1,000.(ABSTRACT TRUNCATED AT 400 WORDS)

The bone marrow micronucleus test and metronidazole genotoxicity in different strains of mice (Mus musculus)

“…In our study the value for the inbred CFW strain ranging from 5.17 to 7.73 (mean 6.45 ± 1.28 for n = 12, Table 1) show partially overlapping within the basal range from 7.50 to 15.00 reported in the literature for this strain (Salamone and Mavourin, 1994). Although a literature search showed no available data for the basal micronucleus frequency of the inbred BALB/cJ strain, our basal value for this strain (mean for 7.70 ± 1.65 for n = 12, Table 1) ranging from 6.05 to 9.35 fell in the superior value of the range between 1.00 to 7.00 reported in the literature for the closely related BALB/c strain (Salamone and Mavourin, 1994).…”

“…However, our basal range for the outbred NIH strain (mean for 7.70 ± 1.65 for n = 12, Table 1) ranging from 7.26 to 11.22 showed no correspondence with the value of 1.7 to 6.1 reported in the literature for this strain (Salamone and Mavourin, 1994). Such a discrepancy could be due to breeding inside the NIH strain colonies, which could have lead to divergence in different breeding centers due to the degree of homogeneity reached inside the colonies in a relatively reduced population of mice (Salamone and Mavourin, 1994). However, the difference in the micronucleus frequency between the inbred and outbred strains (CFW or BALB/cJ versus NIH) was significantly higher (p < 0.05) than that observed between the inbred strains alone (CFW versus BALB/cJ).This could be due to the genetic variability generated when performing each type of crossing.…”

“…Although a literature search showed no available data for the basal micronucleus frequency of the inbred BALB/cJ strain, our basal value for this strain (mean for 7.70 ± 1.65 for n = 12, Table 1) ranging from 6.05 to 9.35 fell in the superior value of the range between 1.00 to 7.00 reported in the literature for the closely related BALB/c strain (Salamone and Mavourin, 1994). However, our basal range for the outbred NIH strain (mean for 7.70 ± 1.65 for n = 12, Table 1) ranging from 7.26 to 11.22 showed no correspondence with the value of 1.7 to 6.1 reported in the literature for this strain (Salamone and Mavourin, 1994). Such a discrepancy could be due to breeding inside the NIH strain colonies, which could have lead to divergence in different breeding centers due to the degree of homogeneity reached inside the colonies in a relatively reduced population of mice (Salamone and Mavourin, 1994).…”

“…More recently, Genetics and Molecular Biology, 30, 4, 1139-1143(2007 Copyright by the Brazilian Society of Genetics. Printed in Brazil www.sbg.org.br however, Salamone and Mavourin (1994) reported that the basal micronucleus frequency of different mice strains diverge significantly from that of their parental strains.…”

“…The experimental models proposed for these evaluations include different strains of inbred, outbred or hybrid mice (Salamone and Mavourin, 1994), transgenic mice (Recio et al, 2005) and, more recently, wildlife animal models (Da Silva et al, 2000 a, b). The species employed to monitor the potential genotoxic effect must be considered as a source of variability as certain genotoxic agents have been described as species-specific.…”