Anthramycin, an antitumor
antibiotic produced by Streptomyces refuineus, produces a well defined covalent adduct with
DNA and lies within the narrow groove of
DNA, attached through a thermal-labile covalent animal linkage to the exocyclic amino group of
guanine, without detectable distortion of the helix (Petrusek, R. L., Anderson, G. L., Garner, T. F., Fannin, Q. L., Kaplan, D. J. Zimmer, S. G., and Hurley, L. H. (1981) Biochemistry 20, 1111-1119). This paper described results in which the
biological consequences of DNA damage and repair by repair-proficient and a repair-deficient
xeroderma pigmentosum (XP 12RO) cell line are presented.
Anthramycin has been shown to produce excision-dependent single and double strand breaks in
DNA, both of which appear to persist many hours after removal of the
drug from the media. The lower ability of the
xeroderma pigmentosum cell line to remove ability of the
xeroderma pigmentosum cell line to remove
anthramycin lesions from
DNA is correlated with a decreased cell survival. The
biological consequences of DNA damage (genetic effects,
DNA strand breakage, and cytotoxicity) are discussed with respect to the defined structure and stability of the
anthramycin-
deoxyguanosine adduct.