{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:07:44Z","timestamp":1761311264291,"version":"3.41.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:00:00Z","timestamp":1500249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>The<jats:italic>Pig\u2010a<\/jats:italic>assay, a recently developed<jats:italic>in vivo<\/jats:italic>somatic gene mutation assay, is based on the identification of mutant erythrocytes that have an altered repertoire of glycosylphosphatidylinositol (GPI)\u2010anchored cell surface markers. We hypothesized that the erythrocyte<jats:italic>Pig\u2010a<\/jats:italic>assay concept could be applied to rat cauda epididymal spermatozoa (sperm) for germ cell mutagenicity evaluation. We used GPI\u2010anchored CD59 as the<jats:italic>Pig\u2010a<\/jats:italic>mutation marker and examined the frequency of CD59\u2010negative sperm using flow cytometry. A reconstruction experiment that spiked un\u2010labeled sperm (mutant\u2013mimic) into labeled sperm at specific ratios yielded good agreement between the detected and expected frequencies of mutant\u2013mimic sperm, demonstrating the analytical ability for CD59\u2010negative sperm detection. Furthermore, this methodology was assessed in F344\/DuCrl rats administered<jats:italic>N<\/jats:italic>\u2010ethyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (ENU), a prototypical mutagen, or clofibrate, a lipid\u2010lowering drug. Rats treated with 1, 10, or 20 mg\/kg body weight\/day (mkd) ENU via daily oral garage for five consecutive days showed a dose\u2010dependent increase in the frequency of CD59\u2010negative sperm on study day 63 (i.e., 58 days after the last ENU dose). This ENU dosing regimen also increased the frequency of CD59\u2010negative erythrocytes. In rats treated with 300 mkd clofibrate via daily oral garage for consecutive 28 days, no treatment\u2010related changes were detected in the frequency of CD59\u2010negative sperm on study day 85 (i.e., 57 days after the last dose) or in the frequency of CD59\u2010negative erythrocytes on study day 29. In conclusion, these data suggest that the epidiymal sperm<jats:italic>Pig\u2010a<\/jats:italic>assay in rats is a promising method for evaluating germ cell mutagenicity. Environ. Mol. 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