Cellular uptake, transport, and macromolecular binding of benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene by human cells in vitro.

Patterns of benzo(a)pyrene (BP) and 7,12-dimethyl benz(a)anthracene(DMBA)uptakeand subcellulardistri butionby monolayerculturesof preconfluenthumanneo natal foreskinfibroblastswere significantlydifferent;the maximumconcentrationof DMBA in the whole-cell frac tion was 6% of the maximum BP concentrationin that fraction, and the maximum DMBA concentrationin the nuclearfractionwas 2% that of maximumnuclear-associ ated BP. Approximately30% of BP present in the cyto plasm of human fibroblasts was bound DMBA. In BP treated cells the extent of polynuclearhydrocarbonup take by the boundcytoplasmicand nuclearfractionswas approximatelythe same; BP appeared first in the bound cytoplasmic fraction and then in the nuclear fraction. The bindingof BP to cytoplasmicproteinand translocationof this bound polynuclearhydrocarbonto the nucleus ap peared to be a functionof one or several metabolitesof the parenthydrocarbon.In DMBA-treatedcellsthe paftern and extent of uptake by the crude cytoplasmicfraction was approximatelythe same as that of the nuclear frac tion, indicating random dispersal of DMBA throughout the cell. Microelectrophoresisof a cell extractpreparedfrom (3H]BP-treatedhuman neonatal foreskincells suggested that the [3H]BP-cytoplasmicproteinassociationwas non covalent.