DNA adduct formation by alachlor metabolites
The extent of DNA adduct formation by alachlor (ArN(CH/sub 2/OCH/sub 3/)C(O)CH/sub 2/Cl wherein Ar is 2,6-diethylphenyl) and its metabolites is used as a guide to deduce the causal agent(s) in the carcinogenicity of this major herbicide. (/sup 14/C-phenyl)Alachlor is compared to its two metabolic cleavage products, (/sup 14/C-phenyl) 2-chloro-N-(2,6-diethylphenyl)acetamide (CDEPA) (ArNHC(O)CH/sub 2/Cl) and (/sup 14/C-phenyl)2,6-diethylaniline (DEA) (ArNH/sub 2/), and to (/sup 14/C-methoxy)alachlor in various in vitro and in vivo systems. Horseradish peroxidase and hydrogen peroxide activate DEA, but not CEDPA or alachlor, for formation of adducts with calf thymus DNA, which probably involves 2,6-diethylnitrosobenzene (ArNO) as an intermediate. Mouse liver microsomes and NADPH are both required to enhance the binding from each labeled preparation to calf thymus DNA; 4-fold higher labeling is observed from (/sup 14/C-methoxy)- than from (/sup 14/C-phenyl)alachlor. This 4-fold preferential DNA labeling from the /sup 14/C-methoxy compound is likewise found in the liver of mice treated intraperitoneally. Mouse liver protein and hemoglobin are also labeled, in vivo, with (/sup 14/C-phenyl)alachlor, -CDEPA and -DEA, and, as with the DNA, the labeling of these proteins is 1.5- to 2-fold higher with (/sup 14/C-methoxy)alachlor.
- Research Organization:
- Univ. of California, Berkeley (USA)
- OSTI ID:
- 6043296
- Journal Information:
- Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 43:25; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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ADDUCTS
ANIMALS
BIOSYNTHESIS
BODY
CALVES
CARBON 14 COMPOUNDS
CARCINOGENESIS
CATTLE
CELL CONSTITUENTS
DIGESTIVE SYSTEM
DNA ADDUCTS
DOMESTIC ANIMALS
GLANDS
HERBICIDES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIVER
LYMPHATIC SYSTEM
MAMMALS
METABOLISM
METABOLITES
MICE
MICROSOMES
ORGANOIDS
ORGANS
PATHOGENESIS
PESTICIDES
RODENTS
RUMINANTS
SYNTHESIS
THYMUS
TRACER TECHNIQUES
VERTEBRATES