Comprehensive macroscopic, histopathological and molecular assessment of B[a]P and NNK-induced lung tumours in A/J mice reveals no chemopreventive efficacy of Thearubigins.

[BACKGROUND] Tobacco smoke is a complex carcinogen mixture, with Benzo[a]pyrene (B[a]P) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone NNK being key contributors to lung carcinogenesis. While chemopreventive strategies using natural compounds such as polyphenols have shown promise, data on post-treatment efficacy, particularly against combined exposure to multiple carcinogens, remain limited.

[METHODS] We employed a lung carcinogenesis model using A/J mice exposed to B[a]P, NNK, or both and systematically tracked tumour burden and transformation risk at 5 and 9-month endpoints. Tumour incidence, multiplicity, and histopathological transformation (hyperplasia, atypical adenomatous hyperplasia-AAH, and adenocarcinoma) were analysed. Thearubigins, a major polymeric polyphenol fraction from black tea, were tested for chemopreventive potential at 1.5 % and 10 % doses.

[RESULTS] At 9 months, a marked increase in transformation risk and confirmed adenocarcinomas was observed compared to 5 months, particularly in the B[a]P + NNK combination group. Treatment with Therabigins did not significantly reduce tumour number or multiplicity across groups. Western blot analysis of key tumorigenesis markers (PCNA, COX-2, BAX, BCL-XL) corroborated with tumorigenesis data.

[CONCLUSION] Thearubigins were ineffective as post-treatment chemopreventive agents against B[a]P and NNK-induced lung carcinogenesis in A/J mice. These findings underscore the importance of using multi-carcinogen models to more accurately reflect clinical risk in studies of carcinogenesis and chemoprevention.