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© 1990 Oxford University Press

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Effects of Recombinant Murine Interferon-{gamma} on Pregnant Mice and Their Fetuses

IKUO KATO*,1, SHIGEKI KIMURA*, TADAKAZU FURUHASHI*, HIROSHI NAKAYOSHI*, SATOSHI TAKAYAMA{dagger} and NORIAKI UENISHI{ddagger}

*NRI Life Science Kajiwara, Kamakura, Kanagawa 247, Japan {dagger}Daiichi Seiyaku Research Institute Kitakasai, Edogawa-ku, Tokyo 134, Japan {ddagger}Basic Research Laboratory, Toray Industries Incorporated Tebiro, Kamakura, Kanagawa 248, Japan

Received December 5, 1988; accepted October 30, 1989

Effects of Recombinant Murine Interferon-{gamma} on Pregnant Mice and Their Fetuses. KATO, I., KIMURA, S., FURUHASHI, T., NAKAYOSHI, H., TAKAYAMA, S., AND UENISHI, N. (1990). Fundam. Appl. Toxicol. 14, 658–665. Recombinant murine interferon-{gamma} (Rec-MuIFN-{gamma}) was administered intramuscularly to C3H/HeNCrj mice on Days 6-15 of gestation at dosage levels of 8 x 105, 4 x 106, and 2 x 107 u/kg/day. Dams were killed for examination of fetuses on Day 18 of gestation. Pregnant females that received 2 x 107 u/kg/day of Rec-MuIFN-{gamma} showed uterine bleeding on Days 10–15 of gestation and could not maintain their pregnancy. These dams died on Days 13–17orwerekilled/ieWrem/sonDays 10–15 for examination, and therefore no fetal data were available for this group. In the 2 x 107 u/kg/day group, the mean absolute weights of the lung and spleen increased and the mean absolute weight of the liver, red blood cells (RBC), hematocrit, and hemoglobin decreased significantly. Surviving dams in the 8 x 103 and 4 x 106 u/kg/day groups showed significant increases in the mean absolute weights of the lung, liver, kidneys, and spleen and a decrease in platelet count. Significant increases in the weights of the heart and ovaries and decreases in RBC, hematocrit, and hemoglobin were observed in the 4 x 106 u/kg/day group. Histopathological examination revealed increased extramedullary hema-topoiesis in the spleen of the 4 x 106 and 2 x 107 u/kg/day groups. Fetuses showed no external, visceral, or skeletal malformations and variations caused by the administration of Rec-MuIFN-7 in any of the treated groups. Although a slight but statistically significant decrease in fetal body weight and a delay in ossification were seen in fetuses in the 4 x 107 u/kg/day group, these findings were considered to be the result of maternal toxicity and not fetal toxicity. No fetal effects were observed i n the 8 x 105 u/kg/day group.


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