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In this study, the effects of sodium chromate on the expression of the 78\u2010kDa glucose\u2010regulated protein (GRP78) gene and on general transcription were investigated with respect to the DNA damage induced by this agent. DNA single\u2010strand breaks, DNA\u2010protein cross\u2010links, and chromium\u2010DNA adducts were present in CHO cells immediately after 2 h of treatment with sodium chromate. Subsequently, these types of damage were repaired at different rates. Single\u2010strand breaks were essentially repaired after 8 h. By 24 h posttreatment, no cross\u2010links remained in cells exposed to 30 or 150 \u03bcM chromate, although cells treated with the 300\u2010\u03bcM concentration still contained cross\u2010links at that time. DNA\u2010chromium adducts remained unrepaired for at least 32 h. The moderate constitutive level of GRP78 mRNA was not affected by chromate. Chromate did, however, suppress induction of this gene by tunicamycin in a concentration\u2010 and time\u2010dependent manner. Thirty micromolar sodium chromate (96% survival), which caused the least DNA damage, had no effect on GRP78 induction, general RNA synthesis, or mRNA synthesis. Induction of GRP78 was suppressed immediately and 12 h after treatment with 150 \u03bcM chromate (54% survival), although there was a partial recovery of induction at 24 h after treatment, which correlated with the repair of DNA\u2010protein cross\u2010links. In contrast, both total cytoplasmic RNA and mRNA synthesis were suppressed by approximately 60\u201375% for at least 32 h by 150 \u03bcM chromate. At the 300\u2010\u03bcM concentration (8% survival), where DNA\u2010protein cross\u2010links persisted beyond 24 h, GRP78 induction was totally suppressed for at least 24 h, while total RNA and mRNA synthesis were suppressed by 80\u201390% for at least 32 h. Overall, the effects of chromate on GRP78 induction correlated most closely with the presence of DNA\u2010protein cross\u2010links, but suppression of total RNA and mRNA synthesis correlated with the presence of DNA\u2010chromium adducts. These results indicate that chromate exerts differential effects on the induction of the GRP78 gene and on general transcription. \u00a9 1992 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.2940060409","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T20:44:17Z","timestamp":1172090657000},"page":"270-279","source":"Crossref","is-referenced-by-count":48,"title":["Transcriptional inhibition by carcinogenic chromate: Relationship to DNA damage"],"prefix":"10.1002","volume":"6","author":[{"given":"Francis C. 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