METABOLIC-ACTIVATION AND DNA-ADDUCTS DETECTION AS BIOMARKERS OF CHLORINATED PESTICIDE EXPOSURES

Citation
M. Dubois et al., METABOLIC-ACTIVATION AND DNA-ADDUCTS DETECTION AS BIOMARKERS OF CHLORINATED PESTICIDE EXPOSURES, Biomarkers, 2(1), 1997, pp. 17-24
Citations number
41
Categorie Soggetti
Toxicology
Journal title
ISSN journal
1354750X
Volume
2
Issue
1
Year of publication
1997
Pages
17 - 24
Database
ISI
SICI code
1354-750X(1997)2:1<17:MADDAB>2.0.ZU;2-A
Abstract
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.