Research Article

A Mathematical Model for DNA Damage and Repair

Figure 4

Effects of different concentrations of estrogen and variant haplotypes of CYP1B1 and APE1 on the formation and repair of DNA adducts. (a) Shows the effect of doubling the concentration of E 2 on the number of AP lesions per 105 nucleotides over time using E 2 = 1 (red curve) and E 2 = 2 (blue curve). (b) Shows the effect of variant haplotypes of CYP1B1 and APE1 leading to an increase in the number of AP lesions per 105 nucleotides relative to wild-type enzymes. Each curve uses different assumptions about the kinetic constant, 𝑘 c a t , for the CYP1B1 and APE1 enzymes. The red curve depicts the wild-types with 𝑘 c a t 1 = 1 . 6 (CYP1B1) and 𝑘 c a t 5 = 1 9 2 . 1 6 8 (APE1). The blue curve uses a 30% increase in 𝑘 c a t 1 , keeping 𝑘 c a t 5 = 1 9 2 . 1 6 8 . The green curve employs a 30% reduction in 𝑘 c a t 1 , keeping 𝑘 c a t 5 = 1 9 2 . 1 6 8 . Finally, the purple curve uses both a 30% increase in 𝑘 c a t 1 and a 30% reduction in 𝑘 c a t 5 . (c) Shows the effect of different variant haplotypes of CYP1B1 and APE1 that cause a decrease in the number of AP lesions per 105 nucleotides relative to wild-type enzymes. The wild-type is shown in red, a 30% decrease of CYP1B1 activity with APE1 activity held at its wild-type level in blue, 30% increase of APE1 activity with CYP1B1 activity held at its wild-type level in green, and a 30% decrease in CYP1B1 activity with a 30% increase of APE1 activity in purple.
352603.fig.004a
(a)
352603.fig.004b
(b)
352603.fig.004c
(c)