Uptake of lipophilic carcinogens by plasma lipoproteins. Structure-activity studies

This report describes the interaction between plasma lipoproteins and two hydroxylated metabolites of benzo[a]pyrene, 3-hydroxybenzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol, which differ significantly in lipophilicity. When incubated with plasma, the metabolites of benzo[a]pyrene exhibit a decreasing distribution into the ultracentrifugal lipoprotein fraction (d less than or equal to 1.20) and an increasing distribution into the albumin-rich fraction (d greater than 1.20) as the degree of hydroxylation of the metabolite increases. At saturation, uptake of benzo[a]pyrene by VLDL, LDL and HDL correlates with lipoprotein and total-lipid volume. Uptake of hydroxylated derivatives per lipoprotein total-lipid volume, in general, decreases with increasing hydroxylation. Contrary to this trend, HDL uptake of 3-hydroxybenzo[a]pyrene at saturation is significantly higher than its uptake of benzo[a]pyrene. Uptake of benzo[a]pyrene-7,8-dihydrodiol per total-lipid volume by all of the lipoprotein classes at saturation is considerably lower than their uptake of 3-hydroxybenzo[a]pyrene. Factors in addition to lipid solubility substantially alter lipoprotein uptake of the metabolites.