Several authors have reported the high hepatic incidence of gamma hexa
chlorocyclohexane (gamma HCH), pentachlorophenol (PCP) and hexachlorob
enzene (HCB) which are widely used as pesticides. Their genotoxicity s
tatus was not clearly known and no mutagenic effects, using the Salmon
ella assay, were reported. In the first part of this report, DNA-adduc
t formation is evaluated in three types of cultured hepatic cells (rod
ent, bird and human) as a biomarker of exposure to genotoxic compounds
. gamma HCH-, PCP- and HCB-DNA adducts were analysed, using the sensit
ive P-32-postlabelling assay in its nuclease pi enrichment version. Th
e genotoxicity of lindane and PCP is clearly established. Total DNA-ad
ducts reached a maximum in foetal rat hepatocytes (17 and 15 adducts p
er 10(9) nucleotides) after an exposure to pentachlorophenol and linda
ne respectively After HCB treatment, limited amounts of DNA-adducts we
re found in the different cells used. The finding that DNA adducts wer
e not the same in all species tested might be due to metabolic differe
nces. Each type of cultured cells preferentially express different cyt
ochrome P450 families. These P450s metabolize a wide Variety of xenobi
otics and bioactivate carcinogens into reactive metabolites able to fo
rm DNA-adducts. The objective of the present study was to examine the
possible association between DNA-adduction and particular CYP450 induc
tion. The induced cytochrome P450s were measured by northern blot anal
ysis. In rat and human cells, lindane treatment strongly induces CYP2B
and CYP3A mRNA levels, whereas pentachlorophenol treatment induces CY
P1A, CYP2B and CYP3A.