Nitrosocarbaryl: its effect on human DNA

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.