Molecular Mechanism of Aniline induced bladder cancer

Abstract

The National Institute for Occupational Safety and Health based in Cincinnati, Ohio, reported that an incidence of the bladder cancer risk was 6.5 times higher for workers considered to have definite exposure to ortho‐toluidine and aniline, and 4 times higher for workers with possible exposure among workers employed at a rubber chemical manufacturing plants. Aniline exposure has been shown to cause: i) An increase in iron overload and induction of oxidative stress in the spleen; ii) Enhanced transcriptional and translational up regulation of IL‐1, IL‐6, and TNF‐α. Increased activation of redox‐sensitive transcription factors NF‐κβ and AP‐1. iii) MAPK phosphorylation, AP‐1 activation, and enhanced TGF‐α gene expression. iv) increased expression of heme oxygenase‐1 (HO‐1), contributing pro‐oxidant mechanism, mediated through iron release, accumulation thus leading to oxidative damage. v) Increased expression of cyclins, Cyclin dependant Kinases (CDKs) and phosphorylation of retinoblastoma protein (pRB) protein; vi) Increases in both p‐IKKα and p‐IKK£]. Taken together, it is suggested that above sequence of events could represent the plausible underlying mechanism of aniline exposure induced oxidative stress.