ANTIBODIES TO CARCINOGEN-DNA ADDUCTS IN MICE CHRONICALLY EXPOSED TO POLYCYCLIC AROMATIC-HYDROCARBONS

Antibodies specific for polycyclic aromatic hydrocarbon (PAH)-DNA addu cts have previously been reported in human sera. In this study, we exa mined the association between mixed PAH exposure and PAH-DNA adduct sp ecific antibodies in BALB/c mice. Mice were treated either by i.p. inj ection or by intragastric (i.g.) intubation with a mixture of seven di fferent PAHs [benzo(a)pyrene (BP), benz(a)anthracene (BA), fluoranthen e (FA), dibenz(a,h)anthracene (DBA), 3-methyl-cholanthrene (MC), chrys ene (Ch), benzo(b)fluoranthene (BF)] at three doses (0, 15, 150 mug of each PAH) twice a week for 8 weeks. Sera were screened by direct ELIS A for antibodies recognizing DNA modified by diolepoxides or epoxides of each PAH injected. In i.p. treated mice, the sera were slightly mor e reactive to DNAs modified with diolepoxides of BP, BA, or Ch or an e poxide of DBA than to unmodified DNA. In i.g. treated mice, the sera w ere more reactive to DNAs modified with diolepoxides of BA or BF than to unmodified DNA. For some PAHs, a dose-response effect was observed between sera reactivity to PAH metabolites and the dose of PAH adminis tered. However, there was considerable variation in the immune respons es among individual mice within each treatment group. When tested by c ompetitive ELISA, none of the sera could discriminate between modified and unmodified DNA. This animal study suggests that an assessment of previous carcinogen exposure by measuring DNA adduct-specific antibodi es requires further validation prior to its application to the human m onitoring of carcinogen exposure.