Tumor-promoting activity of phthalate esters estimated by in vitro transformation using Bhas cells

Abstract

The tumor-promoting activity of four phthalate diesters and three monoesters were tested in vitro in a screening assay using a transformed and non transformed BALB/c3T3 cell mixture and in a transformation assay using Bhas cells (v-Ha-ras-transfected BALB/3T3 cells). Di-2-ethylhexyl phthalate (DEHP), di-n-butyl phthalate (DBP), and their monoesters increased cell proliferation in the screening assay. Mono-n-butyl phthalate (MBuP) and mono-2-ethylhexyl phthalate (MEHP) promoted Bhas cell transformation, whereas the activities of DBP and DEHP were weak. The activity of MEHP was about 1/500 that of 12-O-tetra-decanoyl-phorbol-13-acetate. MBuP and MEHP therefore showed tumor-promoting activity, whereas all the other phthalate esters tested, including di-isononyl phthalate, had little or no such activity. In addition, MBuP and MEHP were formed by hydrolysis in Bhas cells exposed to DBP and DEHP for 4 days. We postulate that MEHP plays a role in the slight ability of DEHP to promote cell proliferation.