Chemoprevention of lung carcinogenesis in addicted smokers and ex-smokers

Abstract

Chemoprevention of lung carcinogenesis is one approach to controlling the epidemic of lung cancer caused by cigarette smoking. The target for chemoprevention should be the activities of the multiple carcinogens, toxicants, co-carcinogens, tumour promoters and inflammatory compounds in cigarette smoke. At present there are many agents, both synthetic and naturally occurring, that prevent lung tumour development in well-established animal models. It seems likely that logically constructed mixtures of these agents, developed from the ground up, will be necessary for the prevention of lung carcinogenesis.

Figure 1

A design for evaluating chemopreventive agents against lung tumorigenesis in A/J mice. Lung tumors are induced by weekly gavage doses of NNK + BaP. Intervention can begin during the carcinogen treatment period (shown here at week 4) or afterward. Adenoma can be scored at week 27 and adenocarcinoma at week 44.

Figure 2

Structures of diverse inhibitors of lung carcinogenesis discussed in the paper

Figure 3

Photographs of lungs from two mice, each treated with vehicle (cottonseed oil) only, or a mixture of BaP plus NNK (2 μmol of each, once weekly for 8 weeks, as in Figure 1), or BaP plus NNK and a mixture of PEITC-NAC and myo-inositol in the diet, starting 24h after the 4th administration of BaP plus NNK. The mice were sacrificed 44 weeks after the beginning of the experiment, as in Figure 1.