Effects of cytosine arabinoside, 6-aminonicotinamide, and 6-mercaptopurine riboside on ectoderm and mesoderm of mouse limb buds

Abstract

The effects of cytosine arabinoside, 6‐aminonicotinamide, and 6‐mercaptopurine riboside on the incorporation of [¹⁴C]glucose moieties and [³²P]phosphate into acid‐soluble material and lipids, RNA, DNA, and protein were measured in the dissected mesoderm and ectoderm of mouse limb buds at the 42–45 (day 11) somite stage. Due to the different proliferative capacities of the two tissues the incorporation of the precursors into mesodermal cells was considerably higher than into ectodermal ones. Cytosine arabinoside inhibited the incorporation of the precursor moieties only into DNA, but very early after its application. This effect was more obvious in mesoderm than ectoderm. 6‐Aminonicotinamide interfered only with glucose metabolism, whereas the incorporation of phosphate was not affected. ¹⁴C radioactivity in the various cell components was similarly reduced in mesoderm and ectoderm. 6‐mercaptopurine riboside caused an increased incorporation of precursor material in all fractions studied in the mesoderm as well as in the ectoderm during the first 12 hours. This was succeeded by a dramatic decrease of incorporated ¹⁴C and ³²P radioactivity. Differences of response in the tissues could not be detected with this drug. It is suggested that the malformations of the extremities caused by these antimetabolites may be predominantly attributed to changes in the cell function rather than to gross effects on cell metabolism.