Interaction of gossypol with DNA

Gossypol, a polyphenolic binaphthyl dialdehyde found in cotton seeds, is a dietary mutagen and a potential male contraceptive. Its interaction with DNA was studied using a combination of S(1) nuclease hydrolysis and hydroxyapatite chromatography. Calf thymus DNA treated with increasing concentrations of gossypol showed a decreasing degree of S(1) nuclease hydrolysis. An increased thermal melting temperature of treated DNA was also observed. When native DNA, treated with gossypol, was chromatographed on hydroxyapatite, it eluted with a lower molarity of phosphate buffer, indicating a lower affinity of the DNA-drug complex for hydroxyapatite. When gossypol bound to DNA was removed by extraction with organic solvents, the resulting DNA samples showed increased S(1) nuclease hydrolysis and decreased thermal melting temperatures. These results indicated the formation of strand breaks in DNA. Gossypol was also shown to produce superoxide anion and singlet oxygen in aqueous solution. Strand breakage in DNA by gossypol may be caused by active oxygen species such as hydroxyl radical and singlet oxygen.