DNA in situ sensitivity to denaturation: A new parameter for flow cytometry of normal human colonic epithelium and colon carcinoma Journal Article
| Authors: | Kunicka, J. E.; Darzynkiewicz, Z.; Melamed, M. R. |
| Article Title: | DNA in situ sensitivity to denaturation: A new parameter for flow cytometry of normal human colonic epithelium and colon carcinoma |
| Abstract: | Modal DNA (ploidy) and sensitivity of DNA in situ to denaturation by acid have been analyzed by flow cytometry of 10 colorectal adenomas and 35 adenocarcinonias; 39 normal mucosa samples served as controls. A new method was developed to denature DNA in chromatin of the freshly isolated, intact, and unfixed individual cell nuclei from surgically resected material. The sensitivity of DNA denaturation (7a) was assayed by metachromatic staining with acridine orange and calculated as a ratio of the at index of the tumor sample to the at index of normal mucosa; the at index is that fraction of DNA, following treatment at pH 1.4, that stains metachromatically with acridine orange at pH 2.6. All adenomas were diploid and in nine of 10 the Ta value was close to 1.00, indicating no difference from control specimens in DNA sensitivity to denaturation. Forty-nine% of adenocarcinomas were aneuploid. Forty-six% of adenocarcinomas differed from normal in sensitivity of DNA to denaturation; the Ta value was lower than 0.90 indicating that chromatin of the tumor cells was more resistant to denaturation than control cells. There was no correlation between sensitivity to denaturation of DNA and incidence of aneuploidy. However, there was a correlation between Ta and the pathologically determined stage of disease. There was increased resistance to denaturation in 58% of tumors classified as Dukes9 C/D stage, in 36% of tumors classified as Dukes9 B, and in 20% classified as Dukes9 A stage of the disease. Statistical analysis of these results revealed significant differences between distributions of Ta in noninvasive (Adenomas and Dukes9 A) versus invasive (Dukes9 B and C/D) tumors with level of significance at P = 0.02. The data suggest that acid denaturation of DNA in situ may be a valuable adjunct in assessing the biology of colon cancer. The molecular basis for this phenomenon is discussed. © 1987, American Association for Cancer Research. All rights reserved. |
| Keywords: | adult; aged; aged, 80 and over; comparative study; flow cytometry; adenocarcinoma; colonic neoplasms; in vitro study; adenoma; dna; dna, neoplasm; nucleic acid denaturation; epithelium; colon carcinoma; acridine orange; rectal neoplasms; aneuploidy; colon; colonic polyps; middle age; intestinal mucosa; human; male; female; priority journal; denaturation; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Research |
| Volume: | 47 |
| Issue: | 15 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1987-08-01 |
| Start Page: | 3942 |
| End Page: | 3947 |
| Language: | English |
| PUBMED: | 3607742 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 5 February 2021 -- Source: Scopus |
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