DIFFERENCES IN THE TUMORIGENIC ACTIVITY OF A PURE HYDROCARBON AND A COMPLEX MIXTURE FOLLOWING INGESTION - BENZO[A]PYRENE VS MANUFACTURED-GAS PLANT RESIDUE
Eh. Weyand et al., DIFFERENCES IN THE TUMORIGENIC ACTIVITY OF A PURE HYDROCARBON AND A COMPLEX MIXTURE FOLLOWING INGESTION - BENZO[A]PYRENE VS MANUFACTURED-GAS PLANT RESIDUE, Chemical research in toxicology, 8(7), 1995, pp. 949-954
The tumorigenic activity of manufactured gas plant residue (MGP) was e
valuated in female A/J mice using a F0927 basal gel diet system. Adult
erated diets containing MGP (0.19% or 0.25%) or benzo[a]pyrene (B[a]P;
16 or 98 ppm) were fed for 260 days. A negative control group was mai
ntained on a nonadulterated basal gel diet. Mice dosed with a single i
p injection of 1.79 mg of B[a]P in a tricaprylin vehicle and maintaine
d on a NIH-07 pellet diet were positive controls. In addition, a nontr
eated group of mice and a group dosed with vehicle only were maintaine
d on a NIH-07 pellet diet and used as negative controls. Animal body w
eight and consumption of MGP and B[a]P were monitored throughout the s
tudy. Ingestion of a 0.10 or 0.25% MGP adulterated diet resulted in 70
and 100% of the mice developing lung tumors with a multiplicity of 1.
19 and 12.17 tumors/mouse, respectively. Mice maintained on a 0.10% MG
P diet consumed 0.7 g of MGP containing 1.8 mg of B[a]P while those fe
d a 0.25% MGP diet ingested 1.5 g of MGP containing 4.2 mg of B[a]P. T
he incidence of lung tumors in mice fed only B[a]P was considerably lo
wer than that observed for animals fed a MGP diet. A diet containing 9
8 ppm B[a]P produced a significant incidence of tumor-bearing mice wit
h 52% developing lung tumors. The multiplicity observed in these anima
ls, however, was not significant at 0.59 tumors/mouse. A diet containi
ng 16 ppm B[a]P did not produce a significant tumorigenic response in
lung. Animals fed a 16 or 98 ppm B[a]P diet consumed a total of 11 and
67 mg of B[a]P, respectively. A single ip dose of B[a]P (1.79 mg in 0
.25 mt of tricaprylin) resulted in 100% lung tumorigenesis with a mult
iplicity of 15.79 tumors/mouse. In contrast to observed induction of l
ung tumors, no forestomach tumors were detected in any animal fed a 0.
10 or 0.25% MGP adulterated diet. However, ingestion of a diet contain
ing only 16 or 98 ppm of B[a]P resulted in 20 and 100% ofthe mice deve
loping forestomach tumors, respectively. The multiplicity for forestom
ach tumors was 0.24 and 4.22 tumors/mouse, respectively. The incidence
of forestomach carcinomas in tumor bearing mice was 8 and 52%, respec
tively. The ip administration of 1.79 mg of B[a]P resulted in an 83% f
orestomach tumor incidence having a multiplicity of 1.83 tumors/mouse.
Forestomach carcinomas were induced in 34% of the mice exhibiting for
estomach tumors. These data indicate that chronic ingestion of MGP- or
B[a]P-adulterated diets produces significant differences in the tumor
igenic response of female A/J mouse forestomach and lung tissues.