Infrared spectral models demonstrate that exposure to environmental chemicals leads to new forms of DNA

被引:32
作者
Malins, DC
Polissar, NL
Gunselman, SJ
机构
[1] MT WHISPER LIGHT STAT CONSULTING,SEATTLE,WA 98112
[2] UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195
关键词
free radicals; hydroxyl radical; cancer etiology; Fourier transform infrared spectroscopy; principal components analysis;
D O I
10.1073/pnas.94.8.3611
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Environmental chemicals are known to induce a high degree of hydroxyl radical-mediated damage in DNA. Accordingly, we tested the hypothesis that this exposure leads to new forms of DNA using principal components analysis of Fourier transform infrared spectra. The hepatic DNA of English sole (controls) from an essentially clean environment was compared with that of sole inhabiting a chemically contaminated environment. All livers studied were cancer-free; however, a high incidence of liver cancer has been found in the exposed population. The exposed sole were sampled twice, 2 years apart, while the sediments in which they live were under remediation. After obtaining infrared spectra, the first three principal components (PC1, PC2, and PC3) were calculated and found to represent 97% of the total spectral variance. When the principal component scores were plotted in 3-dimensional space, clusters of points were obtained that represented the DNA from the control and exposed groups. Each of the points was derived from approximate to 10(6) wavenumber-absorbance correlations. The spatial location of a point was a highly discriminating measure of DNA structure. The clusters of points were completely separated, demonstrating that the three groups could be 100% correctly classified. The points from the control group were tightly clustered whereas those from the exposed groups were highly diverse. The findings demonstrate that exposure to environmental chemicals results in new, structurally diverse forms of DNA that likely play an important role in carcinogenesis.
引用
收藏
页码:3611 / 3615
页数:5
相关论文
共 24 条
[1]   RELATING AROMATIC HYDROCARBON-INDUCED DNA-ADDUCTS AND C-H-RAS MUTATIONS IN MOUSE SKIN PAPILLOMAS - THE ROLE OF APURINIC SITES [J].
CHAKRAVARTI, D ;
PELLING, JC ;
CAVALIERI, EL ;
ROGAN, EG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (22) :10422-10426
[2]  
CHENG KC, 1992, J BIOL CHEM, V267, P166
[3]   THE ROLE OF 8-HYDROXYGUANINE IN CARCINOGENESIS [J].
FLOYD, RA .
CARCINOGENESIS, 1990, 11 (09) :1447-1450
[4]   TOXIC DNA DAMAGE BY HYDROGEN-PEROXIDE THROUGH THE FENTON REACTION INVIVO AND INVITRO [J].
IMLAY, JA ;
CHIN, SM ;
LINN, S .
SCIENCE, 1988, 240 (4852) :640-642
[5]   8-HYDROXYADENINE (7,8-DIHYDRO-8-OXOADENINE) INDUCES MISINCORPORATION IN IN-VITRO DNA-SYNTHESIS AND MUTATIONS IN NIH 3T3 CELLS [J].
KAMIYA, H ;
MIURA, H ;
MURATAKAMIYA, N ;
ISHIKAWA, H ;
SAKAGUCHI, T ;
INOUE, H ;
SASAKI, T ;
MASUTANI, C ;
HANAOKA, F ;
NISHIMURA, S ;
OHTSUKA, E .
NUCLEIC ACIDS RESEARCH, 1995, 23 (15) :2893-2899
[6]  
*KING COUNT DEP NA, 1996, DUW DIAG PHAS 2 SAMP
[7]   MISREADING OF DNA TEMPLATES CONTAINING 8-HYDROXYDEOXYGUANOSINE AT THE MODIFIED BASE AND AT ADJACENT RESIDUES [J].
KUCHINO, Y ;
MORI, F ;
KASAI, H ;
INOUE, H ;
IWAI, S ;
MIURA, K ;
OHTSUKA, E ;
NISHIMURA, S .
NATURE, 1987, 327 (6117) :77-79
[8]   THE ETIOLOGY OF CANCER - HYDROXYL RADICAL-INDUCED DNA LESIONS IN HISTOLOGICALLY NORMAL LIVERS OF FISH FROM A POPULATION WITH LIVER-TUMORS [J].
MALINS, DC ;
HAIMANOT, R .
AQUATIC TOXICOLOGY, 1991, 20 (03) :123-129
[9]   Tumor progression to the metastatic state involves structural modifications in DNA markedly different from those associated with primary tumor formation [J].
Malins, DC ;
Polissar, NL ;
Gunselman, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (24) :14047-14052
[10]   Models of DNA structure achieve almost perfect discrimination between normal prostate, benign prostatic hyperplasia (BPH), and adenocarcinoma and have a high potential for predicting BPH and prostate cancer [J].
Malins, DC ;
Polissar, NL ;
Gunselman, SJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (01) :259-264