Overview of tumor outcomes for all treatments in this study
A. Treatments, survival, and melanocytic tumors | ||||||||||||||||||||||||
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Neonatal treatment, d3 (4, 5) † | Adult treatment, d28-end | Ink4a | Survival (d) | Melanomas | Nevi | |||||||||||||||||||
n−−/n+−/n++‡ | ∑n | ∑n | tm§ | Yield ∥ | ||||||||||||||||||||
Experiment 1A ¶ | ||||||||||||||||||||||||
1: 10 μg DMBA | None | 12/12/0 | 226 | 0 | 59 | 108 * | 0.83 * | |||||||||||||||||
2: 10 μg DMBA | 25 μg TPA 2×/wk | 13/13/0 | 216 | 0 | 133 | 82ns | 2.08ns | |||||||||||||||||
3: 10 μg DMBA | 35.7 J/m2 UV/d | 12/11/0 | 138 | 0 | 47 | 84ns | 0.85 * | |||||||||||||||||
4: 10 μg DMBA | 250 J/m2UV/wk | 7/8/0 | 120 | 0 | 62 | 66 ¶ | 3.00 ¶ | |||||||||||||||||
5: 10 μg DMBA | 375 J/m2 UV/2wk | 11/6/0 | 139 | 0 | 132 | 52 *** | 4.71ns | |||||||||||||||||
6: 10 μg DMBA | 375 J/m2 UV/2wk | 0/8/16 | 160 | 1 | 142 | 62ns | 3.74ns | |||||||||||||||||
Experiment 1B †† | ||||||||||||||||||||||||
7: None | None | 13/15/0 | 284 | 0 | 16 | 432 *** | 0.00 *** | |||||||||||||||||
8: 250 J/m2 UV | None | 8/7/0 | 256 | 0 | 13 | 300 *** | 0.13 ** | |||||||||||||||||
9: None | 375 J/m2 UV/2wk | 13/6/0 | 190 | 0 | 48 | 146ns | 0.21ns | |||||||||||||||||
10: 250 J/m2 UV | 375 J/m2 UV/2wk | 10/8/0 | 171 | 0 | 48 | 88 ** | 0.83 †† | |||||||||||||||||
11: 250 J/m2 UV | 35.7 J/m2 UV/d | 7/11/6 ‡‡ | 143 | 0 | 23 | 152 ‡‡ | 0.61 * | |||||||||||||||||
Experiment 2 §§ | ||||||||||||||||||||||||
12: 100 μg DMBA | 3,000 J/m2 UV/2wk | 7/12/0 | 140 | 1 | 808 | 51 *** | 32.6 *** | |||||||||||||||||
13: 2,000 J/m2 UV | 3,000 J/m2 UV/2wk | 14/13/0 | 235 | 1 | 53 | 205ns | 0.26ns | |||||||||||||||||
14: None | 3,000 J/m2 UV/2wk | 9/11/0 | 254 | 3 | 53 | 195 §§ | 0 §§ | |||||||||||||||||
15: 10 μg DMBA | 375 J/m2 UV/2wk | 4/6/7 | 229 | 0 | 18 | 133ns | 0ns | |||||||||||||||||
B. Outcomes of nonmelanocytic tumors | ||||||||||||||||||||||||
Treatment ∥∥ | Papillomas | Cysts | SCCs | Sarcomas | GL | OT | ||||||||||||||||||
∑n | tm | Yield ∥ | ∑n | tm | Yield ∥ | ∑n | tm | ∑n | tm | ∑n | ∑n | |||||||||||||
1 | 74 | 133 ** | 0.67ns | 19 | 175ns | 0.33ns | 3 | 448 ** | 1 | — *, ¶¶ | 12 | 12 | ||||||||||||
2 | 212 | 82ns | 2.50ns | 10 | —ns | 0.27ns | 4 | — ** | 3 | — ** | 5 | 6 | ||||||||||||
3 | 287 | 98ns | 0.82ns | 9 | 172ns | 0.13ns | 13 | 158ns | 4 | — * | 7 | 11 | ||||||||||||
4 | 64 | 66 ¶ | 2.08 ¶ | 2 | — ¶ | 0 ¶ | 5 | 186 ¶ | 5 | 175 ¶ | 2 | 6 | ||||||||||||
5 | 109 | 80ns | 1.00ns | 6 | 238ns | 0.12ns | 8 | —ns | 5 | 224ns | 3 | 10 | ||||||||||||
6 | 245 | 90ns | 1.42ns | 2 | —ns | 0.05ns | 6 | 253ns | 0 | —ns | 5 | 4 | ||||||||||||
7 | 5 | — *** | 0.00 ** | 17 | 408ns | 0.04ns | 1 | — * | 1 | — ** | 13 | 9 | ||||||||||||
8 | 14 | 287 *** | 0.33ns | 40 | 115ns | 1.67 * | 1 | — * | 1 | — * | 9 | 3 | ||||||||||||
9 | 94 | 111ns | 1.58ns | 24 | 133ns | 0.63ns | 5 | 275ns | 0 | — * | 8 | 5 | ||||||||||||
10 | 93 | 102 †† | 1.50 †† | 9 | — †† | 0.44 †† | 3 | 285 †† | 6 | 336 †† | 10 | 10 | ||||||||||||
11 | 183 | 96 * | 3.00 ** | 42 | 103 ** | 1.17ns | 16 | — * | 1 | — | 4 | 1 | ||||||||||||
12 | 707 | 51 *** | 31.1 *** | 26 | 167ns | 0.63ns | 5 | 385ns | 19 | 153 *** | 6 | 10 | ||||||||||||
13 | 27 | 275ns | 0ns | 114 | 83 *** | 2.04 *** | 0 | —ns | 20 | 282 ** | 3 | 6 | ||||||||||||
14 | 102 | 231 §§ | 0.05 §§ | 25 | 175 §§ | 0 §§ | 9 | — §§ | 5 | — §§ | 8 | 7 | ||||||||||||
15 | 55 | 119 ** | 1.20ns | 5 | — * | 0.20ns | 1 | —ns | 9 | 325 * | 1 | 0 |
NOTE: Levels of significance for yields were obtained by ANOVA and for tumor-free survival by Cox regression (corrected for genotype effects).
Abbreviations: GL, generalized lymphoma; OT, other tumors such as heamangiomas, papillomas of the conjunctiva, lung, brain, and colorectal tumors; ∑n, total number of tumors observed per group; ns, not significant.
↵* DMBA treatment at day 3; UVB treatment at days 3, 4, and 5.
↵† Numbers of Ink4a/Arf knockouts, heterozygotes, and wild types per group. All animals in experiment 1 were Xpa−/−; all animals in experiment 2 were Xpa+/+.
↵‡ tm values were obtained from Kaplan-Meier plots.
↵§ Yields were compared at 98 days (experiment 1A) or 140 days (experiments 1B and 2).
↵∥ For statistics, the group exposed weekly to 250 J/m2 UV was used as reference group.
↵¶ Level of significance of <0.05.
↵** Level of significance of <0.001.
↵†† For statistics, the group exposed neonatally to 250 J/m2 and in adulthood to 375 J/m2 UV per fortnight was used as reference group.
↵‡‡ Level of significance of <0.01.
↵§§ For uniformity, statistical comparisons are based on homozygous knockouts and heterozygotes only.
↵∥∥ For statistics, the group sham exposed neonatally and to 3,000 J/m2 UV per fortnight in adulthood was used as reference group.
↵¶¶ Numbers refer to Table 1A.
↵*** Could not be calculated (percentage of affected animals never reached 50).