The reaction of mono- and di-functional alkylating agents with nucleic acids

Abstract

6. Preliminary figures for androstenol excretion in urine are given. In the age group 18-45 years they ranged from 19 to 2630 ,ug./24 hr. in men and from 66 to 1010 ,ug./24 hr. in women. This work was carried out partly during the tenure of a personal grant from the Medical Research Council to B. W. L. B., who wishes to express his gratitude. Our gratefiul thanks are due to Dr J. A. Pollock, Miss S. Johnson and Miss J. Bradley for their invaluable technical assistance, to the many people who provided 24 hr. urine specimens, to Organon Laboratories Ltd. for a generous gift of androsterone, and to the Medical Research Council for samples of steroids from their Reference Collection. Finally we are indebted to Dr C. L. Hewett of Organon Laboratories Ltd. for his suggestions on the route for the preparation of androstenol.

DNA Interstrand Cross-Linking by Epichlorohydrin

“…Whereas HN2 and DEB have a relatively strong preference for the 5′-GNC sequence relative to 5′-GC, the epihalohydrins cross-linked both sites about equally. Interestingly, the 5′-GC sequence has the minimal N7-to-N7 interstrand distance, and was originally proposed to be the exclusive target of cross-linkers containing chains of five or fewer atoms (52). Other early reports proposed that cross-linking between N7 of guanine would be precluded for agents of less than seven carbon atoms in length (22).…”

DNA repair, genome stability and cancer: a historical perspective

“…Working with Peter Brooks, he showed that many classic alkylating agents worked by reacting directly with DNA to form stable chemical adducts that could disrupt the template function of the DNA molecule 10,11 . This led directly to their seminal observation that the carcinogenicity of polycyclic aromatic hydrocarbons -the likely causative agents of scrotal cancer in those chimney sweeps and also the classic carcinogenic components of tobacco smoke -was directly correlated with their ability to form DNA adducts, providing an unambiguous link between the initiation of cancer and chemical changes to DNA 12 .…”

Structure of the 1,4-Bis(2‘-deoxyadenosin-N6-yl)-2S,3S-butanediol Intrastrand DNA Cross-Link Arising from Butadiene Diepoxide in the Human N-ras Codon 61 Sequence

“…The genotoxicity is probably due to its potential to form DNA-DNA (43)(44)(45)(46) and DNA-protein cross-links (47,48), the latter having been observed in mice (49,50). Mice possess greater sensitivity to butadiene exposure than rats, and this is attributed to their efficient oxidation of BD to BDO 2 (51,52), presumably facilitating DNA cross-linking.…”