Table I.
Lung and pancreatic lesions in male F-344 rats given (S)-NNAL, (R)-NNAL, NNK or racemic NNAL in their drinking water
Control | (R)-NNAL, 5 ppm | (S)-NNAL, 5 ppm | NNK, 5 ppm | Racemic NNAL, 10 ppm | ||||
---|---|---|---|---|---|---|---|---|
A. Tumor incidence | ||||||||
No. of rats necropsied | 22 | 24 | 22 | 24 | 15 | |||
No. of rats with histologically confirmed lung lesions | ||||||||
Hyperplasia | 0 | 24 | 22 | 24 | 15 | |||
Adenoma | 0 | 23 | 22 | 24 | 15 | |||
Carcinoma | 0 | 6a | 10a | 17a,b | 15a | |||
Tumor incidence | 0 | 23c | 22c | 24c | 15c | |||
No. of rats with thoracic cavity tumors | 0 | 2 | 2 | 6 | 9 | |||
No. of rats with metastasis to pancreas | 0 | 1d | 2e | 3f | 4g,h | |||
Gross lung lesion score | Number of rats with lesions | Number of rats evaluated | ||||||
0 | 1 | 2 | 3 | 4 | ||||
B. Gross lung lesion scores | ||||||||
Control | 21 | 0 | 0 | 0 | 0 | 0 | 21i | |
(R)-NNALj | 0 | 6 | 16 | 1 | 0 | 23 | 23 | |
(S)-NNAL | 0 | 2 | 17 | 3 | 0 | 22 | 22 | |
NNKj | 0 | 0 | 9 | 11 | 3k | 23 | 23 | |
Racemic NNAL | 0 | 0 | 4 | 8 | 3 | 15 | 15 |
a P < 0.01 compared with control.
bGreater than (R)-NNAL, P = 0.0015.
c P < 0.0001 compared with control.
dOne rat with two tumors.
eOne rat with one tumor and one rat with two tumors.
fEach rat had one tumor.
gOne rat with one tumor; one with three tumors, one with four tumors and one with six tumors. A total of 14 pancreatic tumors were observed in this group.
h P < 0.05 versus control.
iThe control group had 22 animals, of which one was excluded because of lung lesions attributable to large granular lymphocyte leukemia.
jOne animal in the (R)-NNAL and NNK groups was not scored due to prior sectioning of lungs for histology.
kOverall gross lung lesion score significantly greater than (R)-NNAL (P < 0.0001) and (S)-NNAL (P = 0.0006).