Abstract
Aberrant crypt foci (ACF)induced in the distal colon of F344 male rats, 4, 8, 12 and 35 weeks after the first administration of 1, 2‐dimethylhydrazine‐2HCl (DMH) were examined to determine whether a correlation exists between the nature of goblet cell mucin and the number of crypts (crypt multiplicity) comprising the ACF. According to the ACF score calculated from the results of the qualitative observation of sulfomucins (SuMs) and sialomucins (SiMs), the ACF in the 4th week showed a weak correlation between the nature of the mucus and crypt multiplicity, and the ACF of each class showed similar mucous profiles. From the 8th week, a significant difference (P<0.01) was recognized between the ACF consisting of 3 crypts or less and those consisting of 4 crypts or more. The proportion of crypts with SiM predominance showed a decrease in the 8th.week in the ACF consisting of 1 crypt and in the 12th week in the ACF consisting of 2 or 3 crypts, implying a recovery tendency. The ACF consisting of more than 4 crypts showed little change over time, retaining the tendency of SiM predominance. Ulex europaeus agglutinin‐I (UEA‐I) lectin‐positive crypts appeared in the ACF. This finding was significantly more prominent (P< 0.001) in the ACF with SiM predominance than in the ACF with SuM predominance at each experimental period, and in the 12th week after the first administration of DMH, the incidence of ACF with UEA‐I‐reactive mucin was decreased in the ACF groups consisting of 3 crypts or less, compared with the ACF groups consisting of 4 or more crypts.These results suggest that the biological quality of mucus in ACF consisting of 4 or more crypts is different from that in ACF consisting of 3 crypts or less. This difference should be considered when ACF are used as an intermediate biomarker of colon cancer.
Keywords: Aberrant crypt foci, Rat, Mucus, Ulex europaeus agglutinin I, Crypt multiplicity
Full Text
The Full Text of this article is available as a PDF (599.5 KB).
REFERENCES
- 1. ) Bird , R. P.Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings . Cancer Lett. , 37 , 147 – 151 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Magnuson , B. A. , Carr , I. and Bird , R. P.Ability of aberrant crypt foci characteristics to predict colonic tumor incidence in rats fed cholic acid . Cancer Res. , 53 , 4499 – 4504 ( 1993. ). [PubMed] [Google Scholar]
- 3. ) Qin , X. , Zarkovic , M. , Nakatsuru , Y. , Arai , M. , Oda , H. and Ishikawa , T.DNA adduct formation and assessment of aberrant crypt foci in vivo in the rat colon mucosa after treatment with N‐methyl‐N‐nitrosourea , Carcinogenesis , 15 , 851 – 855 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Lam , L. K. T. and Zhang , J.Reduction of aberrant crypt formation in the colon of CF1 mice by potential chemopre‐ventive agents . Carcinogenesis , 12 , 2311 – 2315 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 5. ) McLellan , E. A. and Bird , R. P.Specificity study to evaluate induction of aberrant crypts in murine colons . Cancer Res. , 48 , 6183 – 6186 ( 1988. ). [PubMed] [Google Scholar]
- 6. ) McLellan , E. A. and Bird , R. P.Effect of disulfiram on 1,2‐dimethylhydrazine‐ and azoxymethane‐induced aberrant crypt foci . Carcinogenesis , 12 , 969 – 972 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Takahashi , M. , Minamoto , T. , Yamashita , N. , Yazawa , K. , Sugimura , T. and Esumi , H.Reduction in formation and growth of 1,2‐dimethylhydrazine‐induced aberrant crypt foci in rat colon by docosahexanoic acid . Cancer Res. , 53 , 2786 – 2789 ( 1993. ). [PubMed] [Google Scholar]
- 8. ) Barrow , B. J. , O'Riordan , M. A. , Stellate , T. A. , Calkins , B. M. and Pretlow , T. P.Enzyme‐altered foci in colons of carcinogen‐treated rats . Cancer Res. , 50 , 1911 – 1916 ( 1990. ). [PubMed] [Google Scholar]
- 9. ) Sandforth , F. , Heimpel , S. , Balzer , T. , Gutschmidt , S. and Riecken , E. O.Characterization of stereomicroscopically identified preneoplastic lesions during dimethylhydrazine‐induced colonic Carcinogenesis . Ear. J. Clin. Invest. , 18 , 655 – 662 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Filipe , M. I.Value of histochemical reactions for muco‐substances in the diagnosis of certain pathological conditions of the colon and rectum . Gut , 10 , 577 – 586 ( 1969. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Dawson , P. A. , Patel , J. and Filipe , M. I.Variations in sialomucins in the mucosa of the large intestine in malignancy: a quantimet and statistical analysis . Histochem. J. , 10 , 559 – 572 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Zusman , I. , Zimber , A. and Nyska , A. , Role of morphological methods in the analysis of chemically induced colon cancer in rats . Acta Anat , 142 , 351 – 356 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Matsushita , Y. , Yamamoto , N. , Shirahama , H. , Tanaka , S. , Yonezawa , S. , Yamori , T. , Irimura , T. and Sato , E.Expression of sulfomucins in normal mucosae, colorectal adenocarcinomas, and metastases . Jpn. J. Cancer Res. , 86 , 1060 – 1067 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. ) Lev , R.A histochemical study of glycogen and mucin in developing human foetal epithelia . Histochem. J. , 1 , 152 – 165 ( 1968. ). [Google Scholar]
- 15. ) Filipe , M. I.Mucous secretion in rat colonic mucosa during Carcinogenesis induced by dimethylhydrazine. A morphological and histochemical study . Br. J. Cancer , 32 , 60 – 77 ( 1975. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. ) Barthold , S. W. and Jonas , A. M.Morphogenesis of early 1,2‐dimethylhydrazine‐induced lesions and latent period reduction of colon Carcinogenesis in mice by a variant of Citrobacter freundii. Cancer Res. , 37 , 4352 – 4360 ( 1977. ). [PubMed] [Google Scholar]
- 17. ) Nakamura , T. , Yonezawa , S. , Tanaka , S. and Sato , E.Lectin histochemistory in colorectal adenomas and early carcinomas (in Japanese) . Pathol. Clin. Med. , 3 , 317 – 322 ( 1985. ). [Google Scholar]
- 18. ) Jass , J. R. , Allison , L. J. , Stewart , S. M. and Lane , M. R.Ulex europaeus agglutinin‐1 binding in hereditary bowel cancer . Pathology , 25 , 114 – 119 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Carraro , S. , Hamamura , S. , Tiscornia , O. , Celener , D. , Celener , F. G. and Fernandez , L. B.Ulex europaeus agglutinin I binding pattern during chemical Carcinogenesis in the rat gastrointestinal tract . Cancer , 72 , 669 – 676 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Yonezawa , S. , Nakamura , T. , Tanaka , S. and Sato , E.Glycoconjugate with Ulex europaeus agglutinin‐I‐binding sites in normal mucosa, adenoma, and carcinoma of the human large bowel . J. Natl Cancer Inst. , 69 , 777 – 785 ( 1982. ). [PubMed] [Google Scholar]
- 21. ) Pretlow , T. P. , O'Riordan , M. A. , Somich , G. A. , Amini , S. B. and Pretlow , T. G.Aberrant crypts correlate with tumor incidence in F344 rats treated with azoxymethane and phytate . Carcinogenesis , 13 , 1509 – 1512 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Spicer , S. S.Diamine methods for differentiating muco‐substances histochemically . J. Histochem. Cytochetn , 13 , 211 – 234 ( 1965. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Caderni , G. , Giannini , A. , Lancioni , L. , Luceri , C. , Biggeri , A. and Dolara , P.Characterisation of aberrant crypt foci in carcinogen‐treated rats: association with intestinal carcinogenesis . Br. J. Cancer , 71 , 763 – 769 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24. ) Kotake , K.Lectin histochemistory of 1, 2‐dimethylhydra‐zine induced rat colonic neoplasia and human colorectal neoplasia (in Japanese) . J. Jpn. Surg. Soc. , 89 , 534 – 546 ( 1988. ). [PubMed] [Google Scholar]
- 25. ) Yonezawa , S. , Nakamura , T. , Tanaka , S. , Kuroki , K. and Sato , E.Lectin histochemistry in a case of ulcerative colitis complicating rectal carcinoma . Acta Pathol. Jpn. , 35 , 1571 – 1579 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 26. ) Kristiansen , E.The role of aberrant crypt foci induced by the two heterocyclic amines 2‐anrimo‐3‐raethyl‐imidazo‐[4,5‐f] quinoline (IQ) and 2‐amino‐l‐methyl‐6‐phenyl‐imidazo[4,5‐b] pyridine (PhIP) in the development of colon cancer in mice . Cancer Lett. , 110 , 187 – 192 ( 1996. ). [DOI] [PubMed] [Google Scholar]