Resistant hepatocytes as early changes in liver induced by polycyclic aromatic hydrocarbons

Induction of putative preneoplastic hepatocytes which are resistant to cytotoxic effect of 2-acetylaminofluorene (2-AAF) by five carcinogenic polycyclic aromatic hydrocarbons (PAH) was tested using gamma-glutamyl transpeptidase (gamma-GT) as a histochemical marker enzyme. Benzo (a) pyrene [B(a)P], 7,12-dimethylbenz(a) anthracene (7,12-DMBA), 3-methylcholanthrene (3-MC), dibenz (a,h)-anthracene [DB(a, h)A] and benzo (a) anthracene [B(a)A] were given 12 h after partial hepatectomy (PH) followed by 2-AAF and carbon tetrachloride (CCI4) feeding, a procedure developed by this laboratory. All of the five PAHs induced a signficantly increased number of gamma-GT positive foci when compared with sham-hepatectomized (SH) or vehicle control groups. The numbers of gamma-GT-positive foci induced by B(as)P, 7,12-DMBA, 3-MC and DB (a,h)A were significantly different from all of the parent compounds, anthracene, naphthalene, pyrene and phenanthrene. B(a)A did not induce significantly increased number of foci only when compared to anthracene. Possible usefulness of this system for in vivo short-term assay is discussed.