Alterations in the Rat Serum Proteome Induced by Prepubertal Exposure to Bisphenol A and Genistein

Humans
are exposed to an array of chemicals via the food, drink
and air, including a significant number that can mimic endogenous
hormones. One such chemical is Bisphenol A (BPA), a synthetic chemical
that has been shown to cause developmental alterations and to predispose
for mammary cancer in rodent models. In contrast, the phytochemical
genistein has been reported to suppress chemically induced mammary
cancer in rodents, and Asians ingesting a diet high in soy containing
genistein have lower incidence of breast and prostate cancers. In
this study, we sought to: (1) identify protein biomarkers of susceptibility
from blood sera of rats exposed prepubertally to BPA or genistein
using Isobaric Tandem Mass Tags quantitative mass spectrometry (TMT-MS)
combined with MudPIT technology and, (2) explore the relevance of
these proteins to carcinogenesis. Prepubertal exposures to BPA and
genistein resulted in altered expression of 63 and 28 proteins in
rat sera at postnatal day (PND) 21, and of 9 and 18 proteins in sera
at PND35, respectively. This study demonstrates the value of using
quantitative proteomic techniques to explore the effect of chemical
exposure on the rat serum proteome and its potential for unraveling
cellular targets altered by BPA and genistein involved in carcinogenesis.