title: Evaluation of the RBC Pig-a assay and the PIGRET assay using benzo[a]pyrene in rats.
abstract: The red blood cell (RBC) Pig-a assay has the potential to detect the in vivo mutagenicity of chemicals. Recently, use of the Pig-a assay with reticulocytes (the PIGRET assay) reportedly enabled the in vivo mutagenicity of chemicals to be detected earlier than using the RBC Pig-a assay. To evaluate whether the PIGRET assay is useful and effective as a short-term test, compared with the RBC Pig-a assay, we performed both assays using benzo[a]pyrene (BP), which is a well-known mutagen. BP was used to dose 8-week-old male rats orally at 0, 75.0, 150, and 300mg/kg administered as a single administration. Peripheral blood samples were then collected on days 0, 7, 14, and 28 after treatment and were used in both assays. In the treatment groups receiving 150mg/kg of BP or more, both the RBC Pig-a assay and the PIGRET assay detected the in vivo mutagenicity of BP. In the 300mg/kg treatment group, in which a significant increase in the mutant frequency (MF) was observed at all the sampling points using both the RBC Pig-a assay and the PIGRET assay, the reticulocyte (RET) Pig-a MF was higher than the RBC Pig-a MF on days 7 and 14 after treatment; nevertheless, the negative control RET Pig-a MF was comparable to the negative control RBC Pig-a MF. In addition, the RET Pig-a MF began to increase after day 7 and reached a maximum value on day 14 after treatment, whereas the RBC Pig-a MF increased continuously from day 7 until day 28 after treatment. These results indicate that the PIGRET assay has a higher sensitivity than the RBC Pig-a assay and that the PIGRET assay is useful for the earlier detection of the in vivo mutagenicity of chemicals, compared with the RBC Pig-a assay.
authors.affiliation: Taisho Pharmaceutical, Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. Electronic address: r-kikuzuki@so.taisho.co.jp.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Kikuzuki
authors.affiliation: Taisho Pharmaceutical, Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Sato
authors.affiliation: Taisho Pharmaceutical, Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Fujiwara
authors.affiliation: Taisho Pharmaceutical, Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Taisho Pharmaceutical, Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ogiwara
authors.affiliation: Taisho Pharmaceutical, Co., Ltd., 1-403, Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Sugiura
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012156:Reticulocytes / Q000187:drug effects*
chemical_list: D008565:Membrane Proteins; D009153:Mutagens; C080086:phosphatidylinositol glycan-class A protein; D001564:Benzo(a)pyrene
keywords: Benzo[a]pyrene; PIGRET assay; RBC Pig-a assay