Comparison of blood protein and target organ DNA and protein binding following topical application of benzo[a]pyrene and 7H-dibenzo[c,g]carbazole to mice

7H-Dibenzo[c,g]carbazole (DBC) induces skin and liver tumorsin mice following topical application, whereas benzo[a]pyrene(BP) induces only skin tumors. DBC also binds to liver DNA toa much greater extent than does BP. The present study examinedfactors that might account for the difference in DNA bindingactivity. [³H]DBC was applied topically to CD-1 mice at dosesof 15, 100 and 1000 nmol/mouse and tissues and blood sampleswere taken 24 h later. Absorption of DBC from skin into bloodand binding to blood proteins occurred linearly with dose. DBCbound to albumin at a 50-fold higher level than to globin andlevels of albumin adducts showed good correlation with levelsof DNA adducts in liver. Hepatic preference over skin in DNAbinding was found to be dose-dependent For comparison of [3H]BPand [3H]DBC binding, doses of 1000 nmol/mouse were used andthe mice were sacrificed at 12, 24 and 48 h. The rate of DBCuptake from skin was 70% higher than for BP over the first 24h, which was reflected in 40-50% higher plasma levels of DBCradiolabel. Skin protein and DNA binding were 2- to 5-fold higherfor BP than DBC. Conversely, total 3H radioactivity levels inliver were 2- to 3-fold higher and liver DNA and protein bindingwere 15- to 20-fold and 3- to 5-fold higher respectively forDBC. Blood protein adduct levels were similar for both chemicals,suggesting that DBC metabolites formed in the liver were tooreactive to re-enter the systemic circulation. Only minor amountsof the radiolabel in the liver were present as the parent compoundsby 12 h after dosing. These results indicate that more rapidabsorption from skin and selective accumulation in the livercontribute to the greater liver DNA binding seen with DBC, butthe types of liver metabolites appear to be the major factoraccounting for the binding difference.