DNA Damaging Agents Increase The Stability of Interleukin 1 alpha, Interleukin 1 beta, and Interleukin 6 Transcripts And The Production Of Relative Proteins.

In this study, we addressed the question of whether carcinogens affected the expression of interleukin-1α (IL1α), interleukin-1β (IL1β), and interleukin-6 (IL6) genes and the production of the relative proteins. Primary cultures of human monocytes were exposed to the alkylating agents mitomycin C (Mit C), methylmethane sulfonate (MMS), and ethylmethane sulfonate (EMS) and tested for the production of IL1α, IL1β, and IL6 proteins, as well as for the expression of IL1α, IL1β, and IL6 transcripts. The production of IL1β and IL6 was significantly augmented by all the three chemicals after 24-48 h of treatment. IL1α was also increased by Mit C and MMS. By Northern blotting analysis, the increased expression of IL1α, IL1β, and IL6 genes was shown to occur at 30 min of Mit C and MMS treatment and to decline after 8 h. Similarly, EMS up-regulated the expression of IL1β and IL6 genes. The mutagen-mediated increase in interleukin transcripts did not require de novo protein synthesis, and it was due to the enhanced half-life of IL1α, IL1β, and IL6 mRNAs rather than to the increased rate of gene transcription. These results suggest that carcinogens, in addition to causing DNA mutations and rearrangements, may also affect cell growth and differentiation by enhancing the expression of cytokine genes.