Reaction products of styrene oxide with guanosine in aqueous media

Abstract

Styrene oxide was reacted with guanosine in fully aqueous conditions, and the products were purified by cation exchange chromatography and h.p.l.c. The products were characterized by u.v. and mass spectra, loss of tritium from the C-8 position and dissociation properties. About 90% of the total product was identified, of which 57, 28 and 15% were assigned to N-7, N2 and O6 adducts. The two diastereomers of beta-substitution accounted for 53% of the N-7 adducts, while the two alpha-substitutions accounted for the remaining 47%. Two species of N2 and O6 products were also isolated but their substitution pattern was not established.

Efficient nonmutagenic replication bypass of DNAs containing β‐adducts of styrene oxide at adenine N6

“…Mutational analysis of styrene oxide-induced mutations in the hprt gene in human T-lymphocytes showed mutations at both GC and AT sites Bastlova and Podlutsky, 1996]. Styrene oxide reacts at many sites in DNA, the ␣or ␤-position of the epoxide, generating a complex array of products [Hemminki and Hesso, 1984;Savela et al, 1986;Latif et al, 1988]. In double-stranded DNA, the major sites of reaction are guanine N7 and adenine N3 [Koskinen et al, 2000]; these adducts are both acid and heat labile and are not expected to persist.…”

Stability of 7‐Alkyldeoxyguanosines of Trichloropropylene Oxide, Epichlorohydrin and Glycidol

“…The respective products were inferred to be 7-(3-trichloro-2-hydroxypropane)deoxyguanosine, 7-(3chloro-2-hydroxypropane)deoxyguanosine, and 7-(2,3-dihydroxypropane)deoxyguanosine, respectively. In each case two diastereomers could be expected as carbon-2 is chiral (Hemminki & Hesso 1984). This was shown for TCPO, whose two diastereomers separated well in the HPLC system used.…”

“…For most of the aliphatic epoxides studied substitution has been shown only through the least substituted oxirane carbon. However, for 3,4-epoxy-l-butene both oxirane carbons have been shown to react (Citti et al 1984) analogous to styrene oxide (Sugiura & Goto 1981;Hemminki & Hesso 1984).…”

An MNDO molecular orbital study of the reactions of protonated oxirane with guanine

“…Interestingly, however, styrene oxide reacts with deoxyguanosine in aqueous solution to give ca. 12% and 28% of the corresponding O6 and N 2 adducts 9 and 10, in addition to products resulting from attack at the 7-position [22]. Moreover, for a number of aryl epoxides derived from polycyclic aromatic hydrocarbons, the corresponding N Z adducts are the major reaction products [ 5 ] .…”