Malachite green induced malignant transformation of syrian hamster embryo (SHE) cells in primary culture: Transformation is associated with enhanced expression of altered p53, bcl-2 and decreased sensitivity to apoptosis

Malachite green (MG) consisting of green crystals with a metallic lustre, i s highly soluble in water, cytotoxic to various mammalian cells and also ac ts as a liver tumor promoter. In view of its industrial importance and poss ible exposure to human beings, MG poses a potential environmental health ha zard. We have previously reported the malignant transformation of Syrian ha mster embryo (SHE) cells by MG. In this study, we have made an attempt to s tudy the effects of MG on the induction of apoptosis in normal and MG trans formed Syrian hamster embryo cells and the expression of altered p53 and bc l-2 immunohistochemically. Induction of apoptosis was detected by flow cyto metry on the basis of G0/G1 hypodiploid peak, Tunel assay and DNA ladder pa ttern. Flow cytometric analysis showed a dose and time dependent induction of apoptosis by MG in control cells whereas induction of apoptosis by MG wa s marginal in transformed cells. Tunel assay and DNA ladder pattern also sh owed decreased apoptosis in transformed cells by MG compared to controls. I mmunostaining studies showed intense staining for p53 in transformed cells whereas no staining was observed in control cells. Also transformed cells s howed overexpression of bcl-2 with exclusive nucelar localization compared to controls which did not show staining. The present study indicated that M G transformed Syrian hamster embryo cells have decreased sensitivity to apo ptosis compared to normal cells and overexpression of altered p53 and bcl-2 seems to be conferring resistance to MG induced apoptosis.