Development of a method to increase the proportion of polychromatic erythrocytes from mouse bone marrow for more rapid evaluation of the micronucleus assay

Selig, Chr.; Schlegelmilch, R.; Wolf, H. U.

doi:10.1016/0165-1161(90)90027-l

Cited by 8 publications

(2 citation statements)

References 5 publications

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“…In order to study the frequency of MN in mouse bone marrow, the femoral cells were flushed out with FCS; the cellular suspension was added on a column of about 2.0 cm height of cellulose Type 50 and x-cellulose and washed out with HBSS solution with a drop speed of 15 drops/ min, according to Selig et al (10).…”

Section: Micronudei (Mn) Analysismentioning

confidence: 99%

Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice.

Hrelia

Maffei

Vigagni

et al. 1994

Environ Health Perspect

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A combined cytogeneticurine metabolite analysis approach was used to assess potential interactive effects between Fenarimol (FN), a fungicide, and trichloroethylene (TRI), a halogenated solvent. FN was demonstrated to selectively induce P450-2B1 isoforms in different organs of treated mice. Since the rate of metabolism and the stereospecificity of metabolism are dependent on the types and amount of P450s available, FN might drastically alter the metabolic activation of a precarcinogen, such as TRI, and its toxicological consequences. Male CD1 mice were divided into untreated, vehicle control, and experimental groups. Animals of the latter groups were treated ip with 150 mg/kg bw FN in corn oil, 457 mg/kg bw TRI in corn oil, TRI plus FN separated by different time intervals. Bone marrow cells were harvested for determination of micronuclei (MN) frequencies in polychromatic erythrocytes (PCE). The presence of the known metabolite of TRI, trichloroethanol (TCE), was quantitated in collected urine by gas chromatography using an electron-capture detector. Linear regression analysis shows that MN frequency by TRI is correlated with TCE concentration in urine. Observed potentiation of genotoxicity of TRI by FN pretreatment (1 hr before TRI treatment) apparently reflects changes in the spectra of enzymes involved in TRI metabolism, and altered toxicokinetic, as witnessed by the 20% difference in TCE excretion from combined treated mice. However, no increased genetic or metabolic effects were observed when FN was administered 3 hr before TRI. No significant interactive effects were observed at a genetic level when FN was administered 1 hr and 3 hr after TRI whereas a 33 to 47% loss in TCE excretion was recorded. On the other hand, concomitant exposure to TRI and FN caused decreased TRI metabolic levels and decreased genetic effects by TRI through its metabolites probably due to an inactivation of microsomal enzymes critical for TRI metabolism. However, exposure to combined treatment at any time interval has an overall genotoxicity lower than that calculated by a simple additivity model.-Environ Health Perspect 102 (Suppl 91:31-34 (1994)

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Section: Micronudei (Mn) Analysismentioning

confidence: 99%

Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice.

Hrelia

Maffei

Vigagni

et al. 1994

Environ Health Perspect

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“…However, it should be noted that other inducers such as alcohols (P-450IIE1) and dioxins (P-450IA2) are promoters also (15,16 peripheral lymphocytes (21) and an assessment of the micronuclei frequency in mouse bone marrow using the acridine orange staining method (22,23 albino CD1 strain) with three different doses of Fenarimol, from 75 to 300 mg/kg body weight, resulted in significant increases of micronucleated erythrocytes (up to 5-fold over the control; p < 0.01), as detected in bone marrow smears (Fig. 2).…”

Section: Introductionmentioning

confidence: 99%

Multiple end point procedure to evaluate risk from pesticides.

Cantelli‐Forti

Paolini

Hrelia

1993

Environ Health Perspect

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Because of the potential environmental impact of pesticides and the large population potentially exposed, the effects of chronic exposure to pesticides need to be determined. Mutagenicity studies have been used to identify specific agents as potential carcinogens or other human health hazards. However, short-term tests are only theoretically correlated to carcinogenesis because their end points can measure only the genotoxic potential ofchemicals, i.e, their activities as initiating agents in multistep carcinogenesis. The objective of our research presented here is to provide a comprehensive examination of the mechanism of toxicity of a series of pesticides. These are substances for which toxicity, at both the genetic and metabolic level, has not been adequately described. Preliminary results on a broad series of compounds belonging to different biological classes (herbicide, insecticide, fungicide) seem to indicate that pesticides are toxic but are poor initiating agents, as shown by negative or weak positive results on different genetic end points (gene mutations, DNA effects, and chromosome aberrations in vitro and in vivo). Immunochemical and biochemical studies, however, seem to indicate the cocarcinogenic and promoting potential of these chemicals. As an example, the genotoxic and biochemical effects induced by Fenarimol (a fungicide) are discussed. The results reported stress the importance of identifying chemicals that act at different levels of the multistep carcinogenesis process to ascertain the risk associated with exposure.

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

Salamone

Mavournin

1994

Environ and Mol Mutagen

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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)

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Development of a method to increase the proportion of polychromatic erythrocytes from mouse bone marrow for more rapid evaluation of the micronucleus assay

Cited by 8 publications

References 5 publications

Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice.

Interactive effects between trichloroethylene and pesticides at metabolic and genetic level in mice.

Multiple end point procedure to evaluate risk from pesticides.

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

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