Preventive agents can block tumor initiation either by blocking
carcinogen activation, by scavenging reactive carcinogens, or
potentially by enhancing DNA damage repair. In addition,
agents can suppress the progression of initiated cells. In this
study, we used the complete chemoprevention protocol, which
involves intervention at 1 to 2 weeks before carcinogen administration.
Preventive agents are used throughout the study.
This protocol is designed to determine both blocking and
suppressing effects on all stages of lung tumorigenesis (initiation,
promotion, and progression). Because the two compounds
are novel agents, deguelin and silibinin were tested
using this protocol based on the rationale that any agent that
was ineffective or minimally effective did not warrant further
consideration at the doses employed. The mice treated with
either deguelin or silibinin showed no signs of gross toxicity or
loss of body weight during the experiment (data not shown).
The administration of deguelin by gavage decreased tumor
multiplicity. The 5-mg/kg dose of deguelin decreased tumor
multiplicity from 7.15 ± 0.72 tumors per mouse (n = 15) in the
control group to 2.64 ± 0.45 tumors per mouse (n = 22, P <
.0001). The higher dose of 10 mg/kg reduced tumor multiplicity
to 3.18 ± 0.44 tumors per mouse (n = 22, P < .0001) (Figure 1).