The nonmutagenic (R)- and (S)-beta-(N(6)-adenyl)styrene oxide adducts are oriented in the major groove and show little perturbation to DNA structure.

Conformations of (R)-beta-(N(6)-adenyl)styrene oxide and (S)-beta-(N(6)-adenyl)styrene oxide adducts at position X(6) in d(CGGACXAGAAG).d(CTTCTTGTCCG), incorporating codons 60, 61 (underlined), and 62 of the human N-ras protooncogene, were refined from (1)H NMR data. These were designated as the beta-R(61,2) and beta-S(61,2) adducts. A total of 533 distance restraints and 162 dihedral restraints were used for the molecular dynamics calculations of the beta-S(61,2) adduct, while 518 distances and 163 dihedrals were used for the beta-R(61,2) adduct. The increased tether length of the beta-adducts results in two significant changes in adduct structure as compared to the corresponding alpha-styrenyl adducts [Stone, M. P., and Feng, B. (1996) Magn. Reson. Chem. 34, S105-S114]. First, it reduces the distortion introduced into the DNA duplex. For both the beta-R(61,2) and beta-S(61,2) adducts, the styrenyl moiety was positioned in the major groove of the duplex with little steric hindrance. Second, it mutes the influence of stereochemistry at the alpha-carbon such that both the beta-R(61,2) and beta-S(61,2) adducts exhibit similar conformations. The results were correlated with site-specific mutagenesis experiments that revealed the beta-R(61,2) and beta-S(61,2) adducts were not mutagenic and did not block polymerase bypass.

Adult laryngeal hemangioma: report of four cases.

Laryngeal hemangiomas in adults are uncommon. We report four such cases seen at our clinic during an 18-month period in 1996 and 1997. All masses were detected by endoscopy, and all were biopsied and ablated uneventfully with a CO2 laser. All four patients recovered without incident. We feel that laryngeal hemangiomas that affect only the glottic area can be treated endoscopically with a CO2 laser without consequences.

Studies of the mechanisms of adduction of 2'-deoxyadenosine with styrene oxide and polycyclic aromatic hydrocarbon dihydrodiol epoxides.

The mechanism of adduction of 2'-deoxyadenosine by styrene oxide and polycyclic aromatic hydrocarbon dihydrodiol epoxides has been explored using (15)N(6)-labeled adenine nucleosides. The extent of reaction at N1 versus N(6) was evaluated by (1)H NMR of the N(6) adducts after allowing Dimroth rearrangement to occur. Products arising from attack at N1 followed by Dimroth rearrangement exhibited a small two-bond (1)H-(15)N coupling constant (N1-H2 J approximately 13 Hz); products from direct attack exhibited a much larger one-bond (1)H-(15)N coupling constant (J approximately 90 Hz). In the case of styrene oxide, all of the N(6) beta adduct arose by initial attack at N1, whereas the majority (70-80%) of the N(6) alpha adducts came from direct attack. The styrene oxide reaction was also studied with a self-complementary oligodeoxynucleotide (24-mer) containing nine (15)N(6)-labeled adenine residues. NMR examination of the N(6) alpha- and beta-styrene oxide adducts isolated after enzymatic degradation of the 24-mer gave very similar results, indicating that N1 attack can occur readily even with a duplexed oligonucleotide. With the PAH dihydrodiol epoxides, only naphthalene dihydrodiol epoxide exhibited significant initial reaction at N1 (50%). No detectable rearranged product was seen in reactions with benzo[a]pyrene dihydrodiol epoxide or non-bay or bay region benz[a]anthracene dihydrodiol epoxide; interestingly, a small amount of N1 attack (5-7%) was seen in the case of benzo[c]phenanthrene dihydrodiol epoxide. It appears that initial attack at N1 is only a significant reaction pathway for epoxides attached to a single aromatic ring.

Rhinophyma: treatment with CO2 laser.

Rhinophyma is an acne rosacea which primarily affects the midface of elderly men, and causes disfigurement as well as obstruction. There are numerous ways of treating this condition and, in our institution, a CO2 laser is the treatment of choice.