Table 4.
Effect of α-Tocopherol on Prostate Carcinogenesis and Non-Neoplastic Prostate Lesions in 17β-Estradiol + Testosterone−Treated NBL Rats
| Group | 1 | 2 | 3 |
|---|---|---|---|
| α-Tocopherol dose (mg/kg diet) | 0 | 2,000 | 4,000 |
| Effective Number of Animals | 29 | 30 | 30 |
| Mortality (weeks after start hormone treatment): | |||
| Mean week of death ± standard deviation | 42 ± 7.3 | 45 ± 6.6 | 42 ± 5.4 |
| Median week of death (95% confidence interval) | 42 (39,45) | 43 (42,47) | 41 (39,43) |
| Range (minimum – maximum) | 27 – 54 | 28 – 52 | 27 – 54 |
| Lesion Incidence | No. (%) of Rats with Lesion: | ||
| Adenocarcinoma: | |||
| Total Cancer Incidence | 26 (90%) | 26 (87%) | 25 (83%) |
| Periurethral dorsolateral-anterior prostatic ducts alone | 22 (76) | 26 (87) | 24 (80) |
| Distal anterior prostate ducts alone | 17 (59) | 22 (73) | 16 (53) |
| Dorsolateral prostate lobe (glandular portion) | 1 (3) | 1 (3) | 0 |
| Tumor Multiplicity: One or two carcinomas | 9 (31) | 6 (20) | 11 (37) |
| More than two carcinomas | 17 (57) | 20 (67) | 14 (47) |
| Carcinoma in situ: | |||
| Anterior prostate (glands & ducts) | 1 (3) | 0 | 1 (3) |
| Seminal vesicle (glands & ducts) | 5 (17) | 7 (23) | 4 (13) |
| Dysplasia in anterior prostate/seminal vesicle (No. animals with lesion/evaluable animals): | |||
| Anterior prostate (glands & ducts) | 6/20 (30) | 12/23 (52) | 12/26 (46) |
| Seminal vesicle (glands & ducts) | 3/20 (15) | 2/23 (9) | 3/26 (12) |
| Inflammation & Dysplasia in Lateral Prostate: | |||
| Inflammation (No. animals with lesion/evaluable animals): | |||
| Total incidence | 29/29 (100) | 30/30 (100) | 30/30 (100) |
| Marked inflammation | 5 (17)a | 3 (10)a | 0a |
| Slight – moderate inflammation | 24 (83)a | 27 (90)a | 30 (100)a |
| Dysplasia associated with inflammation (No. animals with lesion/evaluable animals): | |||
| Total incidence | 23/23 (100) | 26/26 (100) | 26/26 (100) |
| Marked dysplasia | 19 (83)b | 15 (58)b | 10 (38)b |
| Slight – moderate dysplasia | 4 (17)b | 11 (42)b | 16 (62)b |
| Dysplasia not associated with inflammation (No. animals with lesion/evaluable animals): | |||
| Total incidence | 21/22 (100) | 17/22 (100) | 17/26 (100) |
| Marked dysplasia | 8 (36)c | 1 (5)c | 1 (4)c |
| Slight – moderate dysplasia | 13 (59)c | 16 (72)c | 16 (62)c |
| No dysplasia | 1 (5)c | 5 (23)c | 9 (34)c |
Data were tested for significance using Fisher's exact test and for linear trend with dose using a 2 × 3 chi-square test. Differences were considered statistically significant at P ≤ 0.05 (2-sided for Fisher's exact test). Note that for lesions that can only be assessed micropscopically, the number of evaluable animals (with non-autolytic tissue) was often lower than the effective number of animals; the prostate of one rat in the control group was lost to cannibalism, reducing the effective number of animals.
P = 0.0667; P for trend = 0.0205 (chi-square test).
P = 0.0074; P for trend = 0.0018 (chi-square test).
P = 0.0017; P for trend > 0.05, but 0.0017 when combining the slight-moderate and none categories (chi-square test).