OXIDANT-INDUCIBLE ADAPT15 RNA IS ASSOCIATED WITH GROWTH ARREST-INDUCIBLE AND DNA DAMAGE-INDUCIBLE GADD153 AND GADD45

We have recently described a novel RNA, designated adapt15, which is s trongly induced by a pretreatment concentration of hydrogen peroxide i n hamster HA-1 fibroblasts under conditions where a protective ''adapt ive response'' occurs. adapt15 may therefore be involved in protecting cells against the damaging effects of oxidative stress. Since two oth er known sequences, gadd45 and gadd153, were also found to be induced under our pretreatment conditions and are known to be growth arrest an d DNA damage inducible, we decided to also assess the possible associa tion of adapt15 with growth arrest and DNA damage. We found that, like gadd45 and gadd153, the levels of adapt15 RNA were low during prolife ration, but high during density saturation- and low serum (G(0))-growt h arrests. Exposure of HA-1 cells to DNA-damaging agents revealed sign ificant induction of adapt15 RNA by methylmethanesulfonate and cis-pla tinum but not X-irradiation. Near identical responses were also observ ed for gadd45 and gadd153 RNAs, suggesting coordinate regulation of ad apt15, gadd45, and gadd153. All three RNAs were also increased relativ e to control following heat shock, a nongenotoxic treatment. Finally, the induction of adapt15 by hydrogen peroxide was strongly dependent u pon calcium, a hallmark of gadd153 induction. The coordinate induction s of adapt15, gadd45, and gadd153 by multiple agents, and their induct ion by an adaptive- but not by a nonadaptive-response level of hydroge n peroxide, suggest these RNAs may act in concert to protect cells aga inst the damaging effects of oxidative stress. (C) 1996 Academic Press , Inc.