Table 4.
Summary of Kras and Egfr Mutations in Nontumor Lung Tissue and Alveolar/bronchiolar Carcinomas from B6C3F1/N Mice in the 2-Year Inhalation Study of Antimony Trioxidea
| Tissue: | Antimony Trioxide | Mutation Frequencyb |
Kras Codons |
Egfr Exons |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Concentration | Kras | Egfr | 12 | 13 | 14 | 60 | 61 | 18 | 19 | 20 | 21 | |
|
| ||||||||||||
| Nontumor lung: | 0 mg/m3 | 0/10 (0) | 0/10 (0) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Lung tumors: | 0 mg/m3 | 3/9 (33) | 0/9 (0)# | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 3 mg/m3 | 9/28 (32) | 11/28 (39)* | 4 | 0 | 0 | 1 | 4 | 5 | 0 | 4 | 2 | |
| 10 mg/m3 | 15/26 (58) | 11c/26 (42)* | 11 | 0 | 0 | 0 | 4 | 2 | 1 | 8 | 1 | |
| 30 mg/m3 | 10/26 (38) | 15c/26 (58)** | 8 | 1 | 1 | 0 | 0 | 4 | 7 | 4 | 1 | |
|
| ||||||||||||
| All exposed groups combined | 34/80 (43) | 37c/80 (46)** | 23 | 1 | 1 | 1 | 8 | 11 | 8 | 16 | 4 | |
| Without pulmonary overload | 9/28 (32) | 11/28 (39)* | 4 | 0 | 0 | 0 | 4 | 5 | 0 | 4 | 2 | |
| With pulmonary overload | 25/52 (48) | 26c/52 (50)** | 19 | 1 | 1 | 0 | 4 | 6 | 8 | 12 | 2 | |
*
Significantly different (p≤0.05) from the chamber control group by the one-sided Fisher’s exact test.
**
p≤0.005.
#
Significant exposure-concentration trend (p≤0.01) by the Cochran-Armitage trend test.
a
Male and female B6C3F1/N mice were exposed to 0, 3, 10, or 30 mg/m3 antimony trioxide daily by inhalation for 2 years. Silent mutations are not included.
b
Number of tissues with mutation/number of tissues assayed (% with mutation).
c
Same animal with double mutations (M449 with Egfr 20 and 21; M623 with Egfr 19 and 21).