DNA modification in rat lungs following intratracheal or subcutaneous administration of 4-nitroquinoline-1-oxide, benzo[a]pyrene or 2-aminoanthracene.

Benzo[a]pyrene (BP)-, 2-aminoanthracene (2AA)- and 4-nitroquinoline-1-oxide (4NQO)-mediated DNA modification were investigated in rat lungs by using alkaline sucrose gradient sedimentation. The exposure-route, the physicochemical nature of the administered compound and the number of treatments were all important in determining the extent of DNA modification. 4NQO produced qualitatively similar modification whether instilled intratracheally (i.t.) as a suspension or injected subcutaneously (s.c.) in a soluble form. BP and 2AA produced no DNA alteration when injected s.c; they did, however, modify DNA sedimentation when instilled as a suspension, but not until 24 h after treatment. Furthermore, BP caused no DNA modification at any sampling time when instilled in a lipid solvent. In contrast to the DNA modification observed at 24 h after a single i.t. treatment with a BP suspension, no such alteration was detected 12 or 24 h after the last of 5 similar daily treatments. These results are discussed with respect to mechanisms of differential transport, clearance and metabolism of administered carcinogens.