FEASIBILITY STUDY

2-Pyridone as a model system for predicting site-specificity of mutagen attack on DNA

by Ms. Xiang WangMaster of Science ThesisUniversity of MinnesotaRobert M. Carlson AdviserMarch 1994

- HPLC/MS and GC/MS identification of adducts

- Sodium salt of 2-pyridone mixed 1:1 molar ratios

- Acetonitrile media at room temperature

- Measure adduct formation over time (<24 hours)

Electrophile N-Alkylated (10-4)

O-Alkylated (10-4)

O/N Ratio

I odomethane 32.8 ND OIodothane 24.4 3.16 0.132-idopropane 1.33 3.75 2.83Dimethyl sulfate 24.6 4.32 0.17Diethyl sulfate 22.7 9.79 0.43Nitroso methylurea

2.16 17.9 8.3

Nitroso methylurethane

21,0 19.4 0.92

Trimethylphosphite

ND ND ---

Dimethylphosphite

ND ND ---

Trimethylphosphate

ND ND ---

Styrene oxide ND ND ---

Electrophile N-Alkylated (10-4)

O-Alkylated (10-4)

O/N Ratio

Allyl iodide 33.1 3.19 0.097Allyl bromide 26.3 2.46 0.093Allyl chloride 17.3 ND 01,3-dichloro-1-propene

22.8 1.32 0.058

3-chloro-1-butene

0.41 ND 0

3-chlorocyclohexene

0.683 1.03 1.50

benzylchloride 22.3 1.46 0.066Crotyl chloride 1.8 1.51 0.13

Electrophile N-Alkylation(10-4)

O/N Ratio S. Typhimurium mutangenicity

Methyl nitrosourea 2.16 8.32 841Ethyl nitrosourea 3.51 6.11 202Ethylmethylane sulfate

15.6 0.18 1.70

Diethylsufate 22.7 0.43 24.4Dimethyl sulfate 24.6 0.17 5.8Methyl methane sulfonate

33.7 0.036 0.8