904-918Malachite
green (MG), consisting of green crystals with a metallic lustre, is very
soluble in water and is highly cytotoxic to mammalian cells in culture and also
acts as a liver tumour promoter. In view of its industrial importance and
possible
exposure to human beings, MG poses a potential environmental health hazard.
Accordingly, we have studied the effect of MG on the formation of free radicals
using Electron Spin Resonance (ESR) analysis with 5, 5-dimethyl-1-pyrroline N-oxide
(DMPO) as-a spin trapping agent. ESR analysis showed formation of reactive free
radicals during exposure of MG to Syrian hamster embryo (SHE) cells. As per
mechanism-based toxicology in cancer risk assessment, the chemicals that have
the potential to be metabolized to active free radical species could be human
cancer hazards. So, we have investigated
the effect
of MG on the formation of Type II and Type III morphologically transformed foci
using SHE cell transformation assay. MG induced dose related transformed foci.
Some of these transformed foci were taken out using selective
trypsinisation
and established immortal cell lines. One of these immortal cell lines was
characterized extensively. This immortal cell line showed enhanced DNA
synthesis in the form of BrdU incorporation, increased presence of proliferating
cell nuclear antigen (PCNA), bcl-2 and p53 proteins by immunohistochemistry. When
these immortal cells were injected
subcutaneously
into nude mice, they developed tumors which were transplantable and
histopathologically sarcomas. The present studies indicate that MG could be a
potential candidate for two year chemical carcinogenesis rodent bioassays