British Journal of Cancer

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Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon

E T Donnelly, H Bardwell, G A Thomas, E D Williams, M Hoper, P Crowe, W G McCluggage, M Stevenson, D H Phillips, A Hewer, M R Osborne and F C Campbell

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Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Figure 1.

Treatment effects upon MTCRII. (A) Total MT-immunopositive crypt number per 104 crypts in each treatment group. Significant between-group treatment differences were observed (P<0.01). The Duncan post hoc test identified three distinct homogeneous treatment subsets (A–C), showing significant incremental differences in total mutation load: (A) Groups 1–4, distilled water, DMSO or lambdaCgN only (1 and 4%); (B) Groups 5 and 6, MNU only or MNU and one 7 day cycle of 1% lambdaCgN; (C) Groups 8 and 11, MNU and three 7 day cycles of 1% lambdaCgN or MNU and continuous 4% lambdaCgN. Groups 7, 9 and 10 overlapped subsets B and C. (B) Formation of patches of greater than or equal to2 contiguous MT immunopositive crypts in each treatment group. The Duncan posthoc test identified three distinct homogeneous treatment subsets (A–C), showing significant incremental differences in mutant (MT immunopositive) patch formation: (A) Groups 1–4, Distilled water, DMSO or lambdaCgN only (1 and 4%); (B) Group 5, MNU alone; (C) Groups 7 and 9, MNU and one or three 7 day cycles of 4% lambdaCgN. Groups 6, 8, 10 and 11 overlapped subsets B and C. (C) Large MT immunopositive patch. An example of a large patch comprising 5 MT immunopositive crypts, from a combined lambdaCgN/MNU treatment group.

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Figure 2.

Treatment effects on ACF. (A) Effects of treatment regimens on ACF number in murine colon. One-way analysis of variance demonstrated significant between-group differences in numbers of ACF per 104 colonic crypts (P<0.001). The Duncan post hoc test identified 5 homogeneous treatment subsets (A–E), showing significant incremental differences in frequency of ACF formation: (A) Groups 1–4, Distilled water, DMSO or lambdaCgN only (1 and 4%); (B) Group 5, MNU alone; (C) Groups 6 and 7, MNU and one 7 day cycle of 1 or 4% lambdaCgN; (D) Group 8, MNU and three 7-day cycles of 1% lambdaCgN; (E) Groups 9 and 11, MNU and either three 7-day cycles of 4% lambdaCgN or continuous 4% lambdaCgN. These subsets showed significant incremental differences of mean ACF per 104 colonic crypts. Group 10 (MNU and 3 times 7-day cycles of 4% lambdaCgN) overlapped subsets C and D. (B) Effects of treatment regimens on size of ACF (crypt multiplicity). One-way analysis of variance demonstrated significant between-group differences in numbers of aberrant crypts per focus {crypt multiplicity} (P<0.01). The Duncan post hoc test identified 5 homogeneous treatment subsets (A–E), showing significant incremental differences in crypt multiplicity: (A) groups 1 and 2, distilled water alone or DMSO alone; (B) groups 3 and 4, continuous treatment with 1 or 4% lambdaCgN alone; (C) groups 5 and 6, MNU alone or MNU and 1 times 7-day cycle of 1% lambdaCgN; (D) groups 9 and 11, MNU and either 3 times 7-day cycles of 4% lambdaCgN or continuous 4% lambdaCgN; (E) group 8, MNU and three 7-day cycles of 1% lambdaCgN. Groups 7 and 10 (MNU and 1 times 7-day cycle of 4% lambdaCgN or continuous 1% lambdaCgN) overlapped subsets D and E.

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Figure 3.

Correlations between MTCRII and ACF. (A) Total MT-immunopositive crypt number vs number of ACF per 104 crypts. Correlation between total MT-immunopositive crypt number and ACF per 104 crypts in all treatment groups (r=0.732; P<0.01 by Pearson's product moment test). (B) Total MT-immunopositive crypt number vs size of ACF. Correlation between total MT-immunopositive crypt number per 104 crypts and ACF size in all treatment groups (r=0.84; P<0.01 by Pearson's product moment test).

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