Micronucleus test with procarbazine hydrochloride administered by intraperitoneal injection and oral gavage

Inouye, Tatsuo; Imanishi, Hisako; Watanabe, M.; Sasaki, YūF.; Shirasu, Yasuhiko; Ando, Nobuaki; Ishii, Shun-ichiro

doi:10.1016/0165-1218(89)90098-0

Cited by 5 publications

(2 citation statements)

References 7 publications

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“…In addition to mutagenicity, our experiment showed that PCZ also caused significant clastogenic and DNA damage responses in Sprague–Dawley rats, in both short‐term and subchronic treatment protocols. As also is revealed in a number of earlier published studies (almost all conducted in mice) (Wild, ; Inouye et al, ; Romagna and Schneider, ; Vanparys et al, ; Suzuki et al, ; Phonethepswath et al, ), we found a robust induction of micronuclei in both peripheral blood and bone marrow at all analyzed timepoints or upon terminal sacrifice using both treatment regimens. Similarly, the alkaline Comet assay detected significant %tail DNA increases in the liver, kidney, lung, and peripheral blood of PCZ‐treated rats, which is consistent with previous positive findings for these tissue types in PCZ‐treated rodents (Sasaki et al, ; ; Sekihashi et al, ).…”

Section: Discussion and Summarysupporting

confidence: 89%

“…In addition to mutagenicity, our experiment showed that PCZ also caused significant clastogenic and DNA damage responses in Sprague-Dawley rats, in both short-term and subchronic treatment protocols. As also is revealed in a number of earlier published studies (almost all conducted in mice) (Wild, 1978;Inouye et al, 1989;Romagna and Schneider, 1990;Vanparys et al, 1990; Suzuki et al, Environmental and Molecular Mutagenesis. DOI 10.1002/em 1999; Phonethepswath et al, 2013), we found a robust induction of micronuclei in both peripheral blood and bone marrow at all analyzed timepoints or upon terminal sacrifice using both treatment regimens.…”

Section: Procarbazine Hydrochloridementioning

confidence: 68%

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Assessment of the Pig‐a, micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate

Gaofeng

Wen

Zhihui

et al. 2018

Environ and Mol Mutagen

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The utility and sensitivity of the newly developed flow cytometric Pig‐a gene mutation assay have become a great concern recently. In this study, we have examined the feasibility of integrating the Pig‐a assay as well as micronucleus and Comet endpoints into acute and subchronic general toxicology studies. Male Sprague–Dawley rats were treated for 3 or 28 consecutive days by oral gavage with procarbazine hydrochloride (PCZ) or ethyl carbamate (EC) up to the maximum tolerated dose. The induction of CD59‐negative reticulocytes and erythrocytes, micronucleated reticulocytes in peripheral blood, micronucleated polychromatic erythrocytes in bone marrow, and Comet responses in peripheral blood, liver, kidney, and lung were evaluated at one, two, or more timepoints. Both PCZ and EC produced positive responses at most analyzed timepoints in all tissue types, both with the 3‐day and 28‐day treatment regimens. Furthermore, comparison of the magnitude of the genotoxicity responses indicated that the micronucleus and Comet endpoints generally produced greater responses with the higher dose, short‐term treatments in the 3‐day study, while the Pig‐a assay responded better to the cumulative effects of the lower dose, but repeated subchronic dosing in the 28‐day study. Collectively, these results indicate that integration of several in vivo genotoxicity endpoints into a single routine toxicology study is feasible and that the Pig‐a assay may be particularly suitable for integration into subchronic dose studies based on its ability to accumulate the mutations that result from repeated treatments. This characteristic may be especially important for assaying lower doses of relatively weak genotoxicants. Environ. Mol. Mutagen. 60:56–71, 2019. © 2018 Wiley Periodicals, Inc.

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Section: Discussion and Summarysupporting

confidence: 89%

Section: Procarbazine Hydrochloridementioning

confidence: 68%

Assessment of the Pig‐a, micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate

Gaofeng

Wen

Zhihui

et al. 2018

Environ and Mol Mutagen

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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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The in vitro micronucleus test on isolated human lymphocytes

Vian

Bichet

Gouy

1993

Mutation Research/Environmental Mutagenesis and Related Subject

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Micronucleus test with procarbazine hydrochloride administered by intraperitoneal injection and oral gavage

Cited by 5 publications

References 7 publications

Assessment of the Pig‐a, micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate

Assessment of the Pig‐a, micronucleus, and comet assay endpoints in rats treated by acute or repeated dosing protocols with procarbazine hydrochloride and ethyl carbamate

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

The in vitro micronucleus test on isolated human lymphocytes

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