Human skin cells (both normal and
xeroderma pigmentosum) were treated with
carbaryl (N-methyl-1-naphthyl-carbamate), a common agricultural
pesticide, or its N-nitroso derivative,
nitrosocarbaryl, and the
DNA of the cells was sedimented in alkaline
sucrose gradients at several times
after treatment. Numerous single-strand breaks were apparent in the
DNA of the
nitrosocarbaryl-treated cells but not in the
DNA of those treated with
carbaryl. The
nitrosocarbaryl effect on the
DNA could be observed up to 20 h after removal of the chemical from the cultures. The
DNA of human cells treated with ring labeled nitroso[3H]
carbaryl and methyl labeled nitroso[14C]
carbaryl was isolated and banded in
cesium chloride density gradients. The peak of 14C radioactivity and not the 3H radioactivity coincided with the optical density peak of the human
DNA from these gradients. An aliquot of the same
DNA was alkaline denatured and banded on alkaline
cesium chloride gradients with similar results. These observations suggest that the
nitrosocarbaryl molecule is split and only the methyl containing residue forms an irreversible association with human cellular
DNA, resulting in chemical changes observable as
alkali-sensitive bonds.