Benzo[a]pyrene-7,8-diol-9,10-epoxide-DNA adducts and increased p53 protein in mouse skin

p53 protein expression has been shown to increase in responseto DNA damage in cell culture systems. We have Studied p53 expressionand benzoa]pyrene (Ba]P) -induced DNA-damage in the form ofbenzoa]pyrene-7,8-diol-9,10-epoxide (BPDE)-DNA adducts as measuredby synchronous fluorescence spectrophotometry (SFS) in Ba]P-treatedC57BL/6 mouse skin. Polyclonal murine antibody CM5, which iscomparable to human CM1, detecting both wild-type and mutatedprotein, was used. BPDE-DNA adducts reached their maximum at24 h after all dosage regimens, but were very well detectablealso at 12 and 48 h after the treatment, while no adducts weremeasurable at 1 week and thereafter. P53 expression was seenin 9/17(53%) skin samples from mouse treated with 500 µgof Ba]P 12–48 h after the treatment, while all 25 (100%)cases of similarly treated mouse skins were negative after 30weeks of the treatment. Only one positive sample of total 11was found among mice treated with repeated 62.5 µg dosesand this was 24 h after the last treatment. After one 62.5 µgdose all mice were negative. This is the first report of anassociation of p53 protein with DNA damage in vivo and givessupport for the putative function of p53 in cellular defensemachinery towards chemical damage.