title: Tumor-augmenting effects of gestational arsenic exposure on F1 and F2 in mice.
abstract: The consequences of early-life exposure to chemicals in the environment are emerging concerns. Chronic exposure to naturally occurring inorganic arsenic has been known to cause various adverse health effects, including cancers, in humans. On the other hand, animal studies by Dr. M. Waalkes' group reported that arsenite exposure of pregnant F0 females, only from gestational day 8 to 18, increased hepatic tumors in the F1 (arsenite-F1) males of C3H mice, whose males tend to develop spontaneous hepatic tumors later in life. Since this mice model illuminated novel unidentified consequences of arsenic exposure, we wished to further investigate the background mechanisms. In the same experimental model, we identified a variety of factors that were affected by gestational arsenic exposure, including epigenetic and genetic changes, as possible constituents of multiple steps of late-onset hepatic tumor augmentation in arsenite-F1 males. Furthermore, our study discovered that the F2 males born to arsenite-F1 males developed hepatic tumors at a significantly higher rate than the control F2 males. The results imply that the tumor augmenting effect is inherited by arsenite-F2 males through the sperm of arsenite-F1. In this article, we summarized our studies on the consequences of gestational arsenite exposure in F1 and F2 mice to discuss novel aspects of biological effects of gestational arsenic exposure.
authors.affiliation: Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, 305-8506 Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nohara
authors.affiliation: Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, 305-8506 Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, 305-8506 Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Okamura
authors.affiliation: Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, 305-8506 Japan.|Graduate School of Pharmaceutical Science, Tokyo University of Science, Noda, 278-8510 Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Matsushita
authors.affiliation: Department of Domestic Science, Kagoshima Women's College, Kagoshima, 890-8565 Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Takumi
keywords: Arsenic; F2; Gestational exposure; Hepatic tumor; Multigenerational