3-Nitrobenzanthrone (3-NBA), a genotoxic
mutagen found in
diesel exhaust and ambient air pollution and its active metabolite
N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) were tested for initiating and complete carcinogenic activity in the NMRI mouse skin
carcinogenesis model. Both compounds were found to be inactive as either tumour initiators or complete
carcinogens in mouse skin over a dose range of 25-400nmol. Topical application of 3-NBA and N-OH-3-ABA produced
DNA adduct patterns in epidermis, detected by (32)P-postlabelling, similar to those found previously in other organs of rats and mice. 24h after a single treatment of 100nmol
DNA adduct levels produced by 3-NBA (18+/-4 adducts/10(8)
nucleotides) were 6 times lower than those by 7,12-dimethylbenz[a]
anthracene (DMBA; 114+/-37 adducts/10(8)
nucleotides). In contrast, identical treatment with N-OH-3-ABA resulted in adduct levels in the same range as with DMBA (136+/-25 adducts/10(8)
nucleotides), indicating that initial
DNA adduct levels do not parallel tumour initiating activity. When compounds were tested for tumour initiating activity by a single treatment followed by twice-weekly applications of TPA,
DNA adducts formed by DMBA, but not by 3-NBA or N-OH-3-ABA, were still detectable 40weeks
after treatment. When tested for activity as complete
carcinogens by twice-weekly topical application, 3-NBA and N-OH-3-ABA produced identical
DNA adduct profiles in mouse skin, with adducts still detectable after 40weeks. Only 3-NBA produced detectable adducts in other organs.