Age-related radical-induced DNA damage is linked to prostate cancer.
We measured concentrations and ratios of mutagenic (8-OH) lesions to putatively nonmutagenic formamidopyrimidine (Fapy) lesions of adenine (Ade) and guanine (Gua) to elucidate radical (.OH)-induced changes in DNA of normal, normal from cancer, and cancer tissues of the prostate. The relationship between the lesions was expressed using the mathematical model log(10)[(8-OH-Ade + 8-OH-Gua)/(FapyAde + FapyGua)]. Logistic regression analysis of the log ratios for DNA of normal and cancer tissues discriminated between the two tissue groups with high sensitivity and specificity. Correlation analysis of log ratios for normal prostates revealed a highly significant increase in the proportion of mutagenic base lesions with age. Data from correlation analysis of the log ratios for normal tissues from cancer were consistent with an age-dependent, dose-response relationship. The slopes for both correlations intersected at approximately 61 years, an age when prostate cancer incidence is known to rise sharply. The age-related increase in the proportion of.OH-induced mutagenic base lesions is likely a significant factor in prostate cancer development.
Malins
D C
DC
Molecular Epidemiology Program, Pacific Northwest Research Institute, Seattle, Washington 98122, USA. dmalins@pnri.org
Johnson
P M
PM
Wheeler
T M
TM
Barker
E A
EA
Polissar
N L
NL
Vinson
M A
MA
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000367:Age Factors; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism* / Q000633:toxicity; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011467:Prostate / Q000378:metabolism / Q000502:physiology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism
D004273:DNA, Neoplasm; D011743:Pyrimidines; C071023:2,6-diamino-4-hydroxy-5-formamidopyrimidine; C002992:8-hydroxyadenine; D017665:Hydroxyl Radical; C039544:4,6-diamino-5-N-formamidopyrimidine; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D000225:Adenine