Induction of nuclear anomalies in the gastrointestinal tract by polycyclic aromatic hydrocarbons

A selective list of polycyclic aromatic hydrocarbons (PAH) with varied carcinogenic and mutagenic potencies, which are identified as common contaminants at industrial sites and which often contaminate the neighboring ground water, are investigated for their ability to induce nuclear anomalies (NA) in the mouse gastrointestinal (G.I.) tract. These studies examined the hypothesis that a relationship between NA induction and carcinogenic potency of these PAH exists. Among the PAH tested, 7,12-dimethylbenzanthrene (DMBA) was most effective inducer of NA in all G.I. tract tissues examined, with the relative potency in duodenum of DMBA much much greater than benzo[a]pyrene (B[a]P) much greater than benzo[b]fluoranthene (B[b]F). The induction of NA by benzo[a]anthracene (B[a]A), pyrene (PY) and benzo[e]pyrene (B[e]P) was not different from that elicited by vehicle controls. MNU, a known potent inducer of NA in the mouse G.I. tract, yielded a high level of NA in duodenum and proximal colon but was less effective than DMBA in the forestomach. The data suggest that induction of NA by DMBA and B[a]P PAH are in approximate accordance with their relative carcinogenic potency in the gastrointestinal tract. When binary mixtures of some PAH were administered the yield of NA was less than that expected by simple additivity and closer to that expected by averaging the activities of the two PAH comprising the mixture. Thus, this short-term in vivo assay may be useful as a predictor of the genotoxic or carcinogenic strength of individual PAH and/or mixtures of these compounds.