Oxidant-inducible adapt15 RNA is associated with growth arrest- and DNA damage-inducible gadd153 and gadd45

We have recently described a novel RNA, designated adapt15, which is strongly induced by a pretreatment concentration of hydrogen peroxide in hamster HA-1 fibroblasts under conditions where a protective ''adaptive response'' occurs. adapt15 may therefore be involved in protecting cells against the damaging effects of oxidative stress. Since two other known sequences, gadd45 and gadd153, were also found to be induced under our pretreatment conditions and are known to be growth arrest and DNA damage inducible, we decided to also assess the possible association of adapt15 with growth arrest and DNA damage. We found that, like gadd45 and gadd153, the levels of adapt15 RNA were low during proliferation, but high during density saturation- and low serum (G(0))-growth arrests. Exposure of HA-1 cells to DNA-damaging agents revealed significant induction of adapt15 RNA by methylmethanesulfonate and cis-platinum but not X-irradiation. Near identical responses were also observed for gadd45 and gadd153 RNAs, suggesting coordinate regulation of adapt15, gadd45, and gadd153. All three RNAs were also increased relative to control following heat shock, a nongenotoxic treatment. Finally, the induction of adapt15 by hydrogen peroxide was strongly dependent upon calcium, a hallmark of gadd153 induction. The coordinate inductions of adapt15, gadd45, and gadd153 by multiple agents, and their induction by an adaptive- but not by a nonadaptive-response level of hydrogen peroxide, suggest these RNAs may act in concert to protect cells against the damaging effects of oxidative stress. (C) 1996 Academic Press, Inc.