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The effect of 17β-estradiol on mouse micronucleus induction by 2-acetylaminofluorene
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JEMS Abstracts/Mutation Research 334 (1995) 385-427
or benzene (BEN; 125, 250, 500, 1000, or 2000 mg/kg/day) for 14 days. Peripheral blood was sampled before each dosing on days 1, 3, 6, 9, 12 and 15 (24 h after the 14th dosing) for PHE and 6MP, on days 1, 3, 5, 7, 9, 11, 13, 15 for BEN. Peripheral blood was stained supravitally with acridine orange. The frequencies of MNRETs were recorded based on the observation of 1000 reticulocytes per rat. Reticulocytes were restricted to types I and II of the classification by Vander et al. (1963). BEN (2000 mg/kg/day) induced MNPCEs from day 3, and PHE (1000 and 750 mg/kg/day) and 6MP (20 m g / k g / d a y ) from day 6. The results with peripheral blood were the same as those with bone marrow cells. These results suggest that the detection of MNRETs is possible in rats which are being used for repeated dose toxicity tests. 7 Asano, N., Toxicological Research Division, Nitto Denko Corporation, 1-1-2 Shimohozumi, Ibaraki, Osaka 567, Japan The effect of 17[~-estradiol on mouse micronucleus induction by 2-acetylaminofluorene
2-Acetylaminofluorene (2AAF) is a mutagen at many endpoints after metabolic activation in vivo and displays a sex difference in the induction of mouse bone marrow micronuclei (MN). In this study, I present the effect of the sex hormone 17/3-estradiol on MN induction in male mice treated with 2AAF. BDF 1 male mice were treated with 17/3estradiol (0.1-100.0 mg/kg) intraperitoneally once or subcutaneously once or three times, and with 2AAF (150 mg/kg) intraperitoneally at the time of the last treatment with 17/3-estradiol. The MN test was performed using the acridine orange supravital staining method on peripheral blood reticulocytes obtained 48 h after administration of 2AAF. No suppression of micronucleus induction by 2AAF was observed when BDF 1 male mice were treated intraperitoneally with 17/3estradiol once. Subcutaneous treatment with 17/3-estradiol once or three times, however, sig-
nificantly suppressed micronucleus induction by 2AAF (P < 0.01). 2AAF is metabolized to mutagenic N-hydroxy intermediates by cytochrome P-450. Because simultaneous single intraperitoneal treatment of 17/3-estradiol and 2AAF did not suppress the MN incidence, the suppression by both subcutaneous treatment regimens suggests that 17/3-estradiol modifies the mutagenicity through regulation of cytochrome P-450 gene expression but not by directly interacting with 2AAF. The sex differences in response to 2AAF in the mouse MN assay might reflect differences in the expression of cytochrome P-450 as regulated by the sex hormone 17/3-estradiol or its metabolites. 8 Asanoma, M. a, K. Takahashi b, M. Miyabe ~ and Y. Kawazoe a, a Nagoya City Public Health Research Institute, Hagiyama-cho, Mizuho-ku, Nagoya and b Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467, Japan Suppressive effects of nordihydroguaiaretic acid on tumor initiation and promotion in mouse skin
It has been reported that nordihydroguaiaretic acid (NDGA), a plant lignan which is used as an antioxidant in fats and oils, inhibited tumor initiation and promotion in two-stage skin tumorigenesis. The present study re-evaluated its potency to inhibit tumor initiation and promotion by repeated treatment. The effect on tumor initiation was examined by treatment with 5 mg NDGA 5 rain prior to topical application of 10 nmol DMBA once a week for 5 weeks, followed by topical application of 5 nmol TPA twice a week for 17 weeks. NDGA slightly reduced the number of tumors on the mouse skin (significant (P < 0.05) only at week 15), but did not affect the percentage of tumorbearing mice. It has, however been reported that NDGA afforded significant protection against tumor initiation by DMBA. The potency of NDGA to inhibit tumor initiation seems to somewhat depend on the schedule of treatment following the application of initiating agent. On the other
JEMS Abstracts/Mutation Research 334 (1995) 385-427
or benzene (BEN; 125, 250, 500, 1000, or 2000 mg/kg/day) for 14 days. Peripheral blood was sampled before each dosing on days 1, 3, 6, 9, 12 and 15 (24 h after the 14th dosing) for PHE and 6MP, on days 1, 3, 5, 7, 9, 11, 13, 15 for BEN. Peripheral blood was stained supravitally with acridine orange. The frequencies of MNRETs were recorded based on the observation of 1000 reticulocytes per rat. Reticulocytes were restricted to types I and II of the classification by Vander et al. (1963). BEN (2000 mg/kg/day) induced MNPCEs from day 3, and PHE (1000 and 750 mg/kg/day) and 6MP (20 m g / k g / d a y ) from day 6. The results with peripheral blood were the same as those with bone marrow cells. These results suggest that the detection of MNRETs is possible in rats which are being used for repeated dose toxicity tests. 7 Asano, N., Toxicological Research Division, Nitto Denko Corporation, 1-1-2 Shimohozumi, Ibaraki, Osaka 567, Japan The effect of 17[~-estradiol on mouse micronucleus induction by 2-acetylaminofluorene
2-Acetylaminofluorene (2AAF) is a mutagen at many endpoints after metabolic activation in vivo and displays a sex difference in the induction of mouse bone marrow micronuclei (MN). In this study, I present the effect of the sex hormone 17/3-estradiol on MN induction in male mice treated with 2AAF. BDF 1 male mice were treated with 17/3estradiol (0.1-100.0 mg/kg) intraperitoneally once or subcutaneously once or three times, and with 2AAF (150 mg/kg) intraperitoneally at the time of the last treatment with 17/3-estradiol. The MN test was performed using the acridine orange supravital staining method on peripheral blood reticulocytes obtained 48 h after administration of 2AAF. No suppression of micronucleus induction by 2AAF was observed when BDF 1 male mice were treated intraperitoneally with 17/3estradiol once. Subcutaneous treatment with 17/3-estradiol once or three times, however, sig-
nificantly suppressed micronucleus induction by 2AAF (P < 0.01). 2AAF is metabolized to mutagenic N-hydroxy intermediates by cytochrome P-450. Because simultaneous single intraperitoneal treatment of 17/3-estradiol and 2AAF did not suppress the MN incidence, the suppression by both subcutaneous treatment regimens suggests that 17/3-estradiol modifies the mutagenicity through regulation of cytochrome P-450 gene expression but not by directly interacting with 2AAF. The sex differences in response to 2AAF in the mouse MN assay might reflect differences in the expression of cytochrome P-450 as regulated by the sex hormone 17/3-estradiol or its metabolites. 8 Asanoma, M. a, K. Takahashi b, M. Miyabe ~ and Y. Kawazoe a, a Nagoya City Public Health Research Institute, Hagiyama-cho, Mizuho-ku, Nagoya and b Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, Nagoya 467, Japan Suppressive effects of nordihydroguaiaretic acid on tumor initiation and promotion in mouse skin
It has been reported that nordihydroguaiaretic acid (NDGA), a plant lignan which is used as an antioxidant in fats and oils, inhibited tumor initiation and promotion in two-stage skin tumorigenesis. The present study re-evaluated its potency to inhibit tumor initiation and promotion by repeated treatment. The effect on tumor initiation was examined by treatment with 5 mg NDGA 5 rain prior to topical application of 10 nmol DMBA once a week for 5 weeks, followed by topical application of 5 nmol TPA twice a week for 17 weeks. NDGA slightly reduced the number of tumors on the mouse skin (significant (P < 0.05) only at week 15), but did not affect the percentage of tumorbearing mice. It has, however been reported that NDGA afforded significant protection against tumor initiation by DMBA. The potency of NDGA to inhibit tumor initiation seems to somewhat depend on the schedule of treatment following the application of initiating agent. On the other