[CANCER RESEARCH 44, 5629-5633, December 1984]
Esophageal Microsomal Metabolism of N-Nitrosomethylbenzylamine in the
Zinc-deficient Rat1
David H. Barch,2 Steven C. Kuemmerle, Paul F. Hollenberg, and Philip M. lannaccone
Departments of Medicine [D. H. B.], Pathology [P. F. H„P. M. I.], and Molecular Biology [S. C. K.J, and Northwestern University Cancer Center [D. H. B., S. C. K.,
P. F. H., P. M. I.], Northwestern University Medical School, Chicago. Illinois 60611
ABSTRACT
Epidemiológica! studies
in China suggest
that dietary zinc
deficiency and environmental exposure to A/-nitrosamine carcin
ogens, such as /V-nitrosomethylbenzylamine
(NMBA), are among
the factors associated with an increased incidence of esophageal
carcinoma in humans. NMBA belongs to a class of nitrosamines
which require activation by the cytochrome P-450-dependent
mixed-function oxidases
in order to be mutagenic. Rats main
tained on a zinc-deficient diet exhibited an increased incidence
of NMBA-induced esophageal carcinoma when compared to rats
on a control diet. The increased tumor formation was associated
with an alteration of the microsomal metabolism of NMBA.
Weanling male Sprague-Dawley
rats were raised on egg protein
diets containing 2.3 ppm zinc (low zinc) or 50 ppm zinc (control
zinc). Analysis of tissues revealed a rapid decline in the levels of
zinc in serum and esophagi of the animals fed the low-zinc diet.
Gastric and hepatic zinc content did not differ significantly be
tween the animals fed the low-zinc diet and the animals fed the
control zinc diet, even after 6 weeks. Microsomes were prepared
from esophageal mucosa,
livers, and forestomachs
from wean
ling animals fed these diets for 3 weeks. The rate of formation
of benzaldehyde
from NMBA by esophageal mucosa! micro-
somes prepared from the rats fed the low-zinc diet was nearly
10-fold higher than that of the rats fed the control zinc diet [0.230
±0.047 (S.E.) versus 0.024 ±0.008 nmol/min/mg microsomal
protein; p < 0.001]. The rate of benzaldehyde
formation by
hepatic micros