We are using the technique of mRNA differential display to identify RNAs that may be important in protecting cells against the damaging effects of oxidative stress. For these studies, we utilize a so-called "adaptive response" model system in which hamster HA-1 cells respond to a minimally toxic "pretreatment" dose of hydrogen peroxide by synthesizing RNAs and proteins that protect them against subsequent exposure to a highly cytotoxic concentration of hydrogen peroxide. Using this approach, we have recently reported several novel RNAs whose levels are increased under conditions of adaptive response. Here we report a new RNA, designated adapt78, whose steady-state level is significantly induced by a pretreatment dose of hydrogen peroxide. adapt78 mRNA was calculated to be 2.35 kb in size and inducible by the standard pretreatment dose of 4 micromol H2O2/10(7) cells. It was induced as early as 90 min after peroxide exposure and maximally at 5 h. Induction was strongly dependent upon calcium. Cloning and sequencing revealed a large predicted open reading frame of 197 amino acids. In vitro transcription and translation generated a protein of 25,000 Da. GenBank homology analysis revealed that much of adapt78 is strongly homologous to a sequence that has been mapped to the Down syndrome critical region (Fuentes et al., Hum. Mol. Genet. 4, 1935-1944, 1995). However, both the 5' and the 3' ends of adapt78 show no homology to any previously reported complete sequence. adapt78 represents a new oxidant-inducible RNA and marker of cellular oxidative stress and may provide new insight into our understanding of oxidant-related disorders and neural degeneration.