DNA repair mechanisms / edited by Philip C. Hanawalt, Errol C. Friedberg, C. Fred Fox.

Date:
1978
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: DNA repair mechanisms / edited by Philip C. Hanawalt, Errol C. Friedberg, C. Fred Fox. Source: Wellcome Collection.

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    8 1. PETER A. CERUTTI 8a, 93-trlhydroxy-7,8,9,lO-tetrahydrobenzo(a)pyrene}yl)deoxy- guanosine (B(a)P-dlol-epoxide II^-dG) (2) the guanine and possibly cytosine adducts formed upon exposure of A549 to the K-region epoxide 4,5-dihydrobenzo(a)pyrene-4,5-epoxide (B(a)P-4,5-epoxide and B(a)P-4,5-epoxide C2) (3) the lesions formed upon reaction of A549 with N-acetoxy-AAF: major lesion 8-[N-(aminofluorenyl)]deoxyguanosine (AAF- (Cg)dG and its deacetylated derivative 8-[N-(aminofluorenyl)] deoxyguanosine (AF- (Cg)dG); minor lesion N^-[3-(2-acetyl- aminofluorenyl)]deoxyguanosine (AAF-(N2)dG)(22). in all these guanine lesions bulky aryl-substituent have been introduced but the position of substitution and the size, stereochemistry and electronic properties of the polycyclic ring systems are different. In a first series of experiments each damaging agent was studied separately and in a second series pairs of damaging agents were studied in the same culture. Under the latter conditions effects of toxicity and cell growth on excisability are the same for the lesions which are being compared and lesion interaction can be investigated. The results of a typical experiment with B(a)P plus N-acetoxy-AAF are given in Figure 1 and 2. Figure 1 shows the chromatographic profiles of DNA digests of A549 cultures which were first treated with [^H]B(a)P for 48 hours, then with [l^C]-N-acetoxy-AAF for 45 min. and subsequently incubated for 0 and 21 hours. The initial levels of damage and the amount of each individual lesion removed as a function of post-treatment incubation is plotted in Figure 2 (it was not possible to measure DNA-acetylation in our experiment). From experiments of this type the following scale of excisa¬ bility of arylation lesions of guanine was derived: (The values listed above the lesions represent the fractions of lesions removed within one generation time under non-saturat¬ ing conditions. Relevant data from other investigators obtained with different human cells is included for compar¬ ison (23-25))^ 1.0 0.80 0.42- B(a)P-4, 5-epoxide > В (a) P-4,5-epoxide » B(a)P-diol- 0.58 0.36 0.17 - 0.32 epoxide II dG > AF - (Cg)dG > B(a)P-diol-epoxide I dG > 0.24 0.22 0.18 B(a)P Bq ^ AAF - (Cg)dG AAF - (N2)dG Skin HeLa Lymph. Raj i AAF-dG 0.23 - 0.40^^^^ BrMeBA - dG 0.26^^^^ AAF - dG 1.0 (?)^^^^
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