Metabolism of 4-hydroxyaminoquinoline-1-oxide and its binding to DNA in chick embryos.
The metabolic pathway of 4-hydroxyaminoquinoline-1-oxide (4HAQO) and its binding to DNA was studied in 2-day chick embryos administered [G-3H]4HAQO in a shell-less culture. The 4HAQO rapidly metabolized into non-carcinogenic compounds and 1 h after administration only very small amounts of free 4HAQO could be detected in the embryo cells. The amount of DNA-bound 4HAQO in the embryo cells reached a maximum 2 h after administration, then began to decrease. The maximum extent (mu mol/mol P of nucleotide) was 18.2, equivalent to 1 molecule of 4HAQO-purine adducts per 2.8 X 10(4) base pairs of DNA. It was possible to detect removal of 4HAQO-purine adducts from DNA in chick embryo cells in a shell-less culture. A dose-response relationship for the killing effect of 4HAQO on 2-day embryos was observed in the range of 0.24-24 nmol 4HAQO per embryo. The practicality of the present method of administration of 4HAQO for 'flash administration' of compounds to chick embryo and the advantages of the shell-less culture method which provides access for biochemical and developmental studies of chick embryos were also discussed.
D015108:4-Hydroxyaminoquinoline-1-oxide / Q000378:metabolism*; D000634:Aminoquinolines / Q000378:metabolism*; D000818:Animals; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism*; D009924:Organ Culture Techniques / Q000379:methods; D013997:Time Factors
D000634:Aminoquinolines; D015108:4-Hydroxyaminoquinoline-1-oxide; D004247:DNA