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Jerome J. Solomon

Jerome J. Solomon

Research Professor, Department of Medicine

biological significance of DNA adducts

Modifying nucleic acids is believed to be the first step in initiating the multi-step carcinogenic process. Mutations are believed to result from specific DNA adducts. Assessing the biological consequences of specific adducts will advance our understanding of somatic mutagenesis. We recently discovered a new class of DNA adducts, 3-hydroxyalkyl uracil residues, which are cytosine alkylation products that undergo a rapid hydrolytic deamination to form a uracil lesion by various environmentally important mutagenic and carcinogenic aliphatic epoxides including ethylene oxide (EO), propylene oxide (PO), and the epoxide of acrylonitrile. 3-Hydroxyalkyl uracil is a potentially mutagenic lesion occupying a central Watson-Crick hydrogen-bonding position and likely to disrupt normal base-pairing. We believe that 3-hydroxyalkyl uracil may be the critical premutagenic lesion produced by aliphatic epoxides in vivo.

We proposed a mechanism (see Figure) involving intramolecular catalysis by the hydroxyl group. We also demonstrated that PO induces mutations at template cytosine residues and that synthesized oligomers containing a single 3-hydroxyethyl uracil lesion induced by EO can be mutagenically bypassed during in vitro DNA polymerization. Our future investigations will focus on the formation and persistence of this lesion in vivo and determine its mutagenic consequences using a site-specific mutagenesis assay in human cells. This research will provide a clearer understanding of the molecular mechanisms relative to how carcinogenesis starts with an environmentally significant class of carcinogens for which the mechanism of somatic mutagenesis is unknown.













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Director of Graduate Studies

Solomon JJ

IARC scientific publications. 1999 Mar; (150):123-35

Singh US; Decker-Samuelian K; Solomon JJ

Chemico-biological interactions. 1996 Jan 05; 99(1-3):109-28

Bhanot OS; Singh US; Solomon JJ

Journal of biological chemistry. 1994 Nov 25; 269(47):30056-64

Palejwala VA; Pandya GA; Bhanot OS; Solomon JJ; Murphy HS; Dunman PM; Humayun MZ

Journal of biological chemistry. 1994 Nov 04; 269(44):27433-40

Bhanot OS; Solomon JJ

Environmental health perspectives. 1994 Sep; 102 Suppl 3:81-90

Snow ET; Singh J; Koenig KL; Solomon JJ

Environmental & molecular mutagenesis. 1994 Dec; 23(4):274-80

Solomon JJ

IARC scientific publications. 1994 Sep; (125):179-98

Solomon JJ; Singh US; Segal A

Chemico-biological interactions. 1993 Sep; 88(2-3):115-35