Table 2

Chemopreventive efficacy of budesonide on BP-induced lung tumorigenesis in A/J mice bearing a dominant negative mutant p53 and/or heterozygous deficiency for Ink4a/Arf

ExperimentGroupNo. of miceGenotypeTreatmentaLung tumor incidenceTumor no./mouseTumor vol. (mm3)Decrease in no.Decrease in vol.
I113p53+/+Ink4a/Arf+/+BP13/13 (100%)7.38 ± 5.443.21 ± 2.77
213p53+/+Ink4a/Arf+/−BP13/13 (100%)7.83 ± 4.732.96 ± 2.08
312p53+/−Ink4a/Arf+/+BP12/12 (100%)12.33 ± 6.277.29 ± 3.98
412p53+/−Ink4a/Arf+/−BP12/12 (100%)12.58 ± 5.097.62 ± 5.79
58p53+/+Ink4a/Arf+/+BP/Bud5/8 (62.5%)1.38 ± 1.69b0.39 ± 0.84b81.3%87.6%
68p53+/+Ink4a/Arf+/−BP/Bud4/8 (50.0%)0.63 ± 0.74b0.17 ± 0.33b92.0%94.3%
78p53+/−Ink4a/Arf+/+BP/Bud7/8 (87.5%)1.71 ± 2.36b0.62 ± 1.19b86.1%91.5%
88p53+/−Ink4a/Arf+/−BP/Bud7/8 (87.5%)2.38 ± 3.16b0.38 ± 0.32b81.1%95.0%
II112p53+/+Ink4a/Arf+/+BP12/12 (100%)11.63 ± 3.2024.09 ± 15.7
215p53+/+Ink4a/Arf+/−BP15/15 (100%)12.00 ± 2.98103.40 ± 123.13
316p53+/−Ink4a/Arf+/+BP16/16 (100%)23.31 ± 5.80218.29 ± 200.31
46p53+/−Ink4a/Arf+/−BP6/6 (100%)27.00 ± 1.55552.39 ± 323.65
519p53+/+Ink4a/Arf+/+BP/Bud17/19 (90%)3.47 ± 2.26b1.51 ± 1.58b69.8%94%c
611p53+/+Ink4a/Arf+/−BP/Bud8/11 (73%)2.72 ± 3.03b1.71 ± 2.56b77.5%98%
718p53+/−Ink4a/Arf+/+BP/Bud18/18 (100%)5.44 ± 2.33b12.54 ± 15.61b76.5%94%
85p53+/−Ink4a/Arf+/−BP/Bud5/5 (100%)9.20 ± 3.70b125.83 ± 79.76b65.9%77%c
III148p53+/+Ink4a/Arf+/+BP48/48 (100%)12.24 ± 4.2617.19 ± 9.99
243p53+/+Ink4a/Arf+/−BP43/43 (100%)12.57 ± 4.7525.03 ± 14.21
335p53+/−Ink4a/Arf+/+BP35/35 (100%)20.72 ± 5.21159.17 ± 170.12
419p53+/−Ink4a/Arf+/−BP19/19 (100%)22.35 ± 5.27414.59 ± 359.07
512p53+/+Ink4a/Arf+/+BP/Bud12/12 (100%)5.70 ± 1.83b3.13 ± 1.65b53.4%81.8%d
68p53+/+Ink4a/Arf+/−BP/Bud8/8 (100%)8.00 ± 2.83b8.97 ± 3.69b36.4%64.2%
710p53+/−Ink4a/Arf+/+BP/Bud10/10 (100%)11.44 ± 3.47b87.11 ± 107.72b44.8%44.6%
86p53+/−Ink4a/Arf+/−BP/Bud6/6 (100%)11.20 ± 4.92b278.57 ± 173.83b49.9%32.8%d
  • a At 6 weeks of age, mice were given single i.p. injections of BP at a dose of 100 mg/kg in tricaprylin, which was counted as week 0. Mice in experiments 1 and 2 were fed with either AIN76A diet or budesonide (1.5 mg/kg) diet 2 weeks before the BP treatment and continued to weeks 18 and 40, respectively. Mice in experiment 3 were fed with either AIN76A diet or budesonide (1.5 mg/kg) diet 12 weeks post-BP treatment and continued to week 30. Approximately equal numbers of males and females were used, with no significant difference in tumor multiplicity between the sexes.

  • b P < 0.01, tumor multiplicity or volume in budesonide groups was significantly different from BP treatment groups.

  • c P = 0.07, tumor volume was decreased in p53+/−Ink4a/Arf+/− mice as compared with their wt littermates.

  • d P < 0.01, tumor volume was decreased in p53+/−Ink4a/Arf+/− mice as compared with their wt littermates.