Quantitation and immunohistochemical localization of DNA adducts in rat embryos and associated yolk sac membranes exposed in vitro to N-acetoxy-2-acetylaminofluorene (N-Ac-AAF).
Specific antibodies and radioimmunoassay (RIA) were used to measure the levels of acetylated and deacetylated C-8 substituted deoxyguanosine adducts in day 11 rat embryos and their associated yolk sacs after exposure of whole rat conceptuses in vitro to the teratogen N-acetoxy-2-acetylaminofluorene (N-Ac-AAF). The deacetylated adduct predominates in both the embryo and the associated yolk sac, and a dose response for adduct formation was observed when adducts were quantitated by RIA. Immunohistochemical localization of the deacetylated adducts revealed that adducts were confined to the nuclei in all tissues examined and that the abundance of adducts varied within and between tissues. Our initial findings indicate that specific DNA adduct antibodies may be useful in the study of teratogenesis induced by a wide variety of agents that modify DNA.
Mirkes
P E
PE
Child Development and Mental Retardation Center, University of Washington, Seattle 98195.
Little
S A
SA
Beland
F A
FA
Huitfeldt
H S
HS
Poirier
M C
MC
D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology*; D000818:Animals; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D004622:Embryo, Mammalian / Q000737:chemistry / Q000187:drug effects*; D005449:Fluorenes / Q000032:analysis*; D009924:Organ Culture Techniques; D011863:Radioimmunoassay; D051381:Rats / Q000196:embryology; D013723:Teratogens / Q000494:pharmacology*; D015017:Yolk Sac / Q000187:drug effects*
D005449:Fluorenes; D013723:Teratogens; C031838:N-(deoxyguanosin-8-yl)-2-aminofluorene; D000099:Acetoxyacetylaminofluorene; D003849:Deoxyguanosine