Influence of FHIT on benzo[a]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N-acetylcysteine

The Ohio State University, Columbus, Ohio, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 06/2006; 103(20):7823-8. DOI: 10.1073/pnas.0601412103
Source: PubMed


The FHIT gene has many hallmarks of a tumor-suppressor gene and is involved in a large variety of cancers. We treated A/J mice and (C57BL/6J x 129/SvJ)F1 (B6/129 F1) mice, either wild-type or FHIT+/-, with multiple doses of benzo[a]pyrene (B[a]P) by gavage. B[a]P caused a time-related increase of micronuclei in peripheral blood erythrocytes. Both A/J and B6/129 F1 mice, irrespective of their FHIT status, were sensitive to induction of forestomach tumors, whereas B[a]P induced glandular stomach hyperplasia and a high multiplicity of lung tumors in A/J mice only. Preneoplastic lesions of the uterus were more frequent in FHIT+/- mice. B6/129 F1 mice underwent spontaneous alopecia areata and hair bulb cell apoptosis, which were greatly accelerated either by FHIT heterozygosity or by B[a]P treatment, thus suggesting that FHIT plays a role in the pathogenesis of alopecia areata. The oral administration of either budesonide or N-acetyl-L-cysteine (NAC) inhibited the occurrence of this inflammatory skin disease. In addition, these agents prevented B[a]P-induced glandular stomach hyperplasia and decreased the size of both forestomach tumors and lung tumors in A/J mice. Budesonide also attenuated lung tumor multiplicity. In B6/129 F1 mice, NAC significantly decreased the proliferating cell nuclear antigen in lung tumors. Both budesonide and NAC inhibited B[a]P-induced forestomach tumors and preneoplastic lesions of the respiratory tract in B6/129 F1 mice. In conclusion, heterozygosity for FHIT affects susceptibility of mice to spontaneous alopecia areata and B[a]P-induced preneoplastic lesions of the uterus and does not alter responsiveness to budesonide and NAC.

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Available from: Roumen Mirtchev Balansky, Jul 24, 2014
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    • "Seven out of 77 total mice were found to have lesions (hyperplasias, adenomas, carcinomas, or in combination) in tissues of the stomach, pancreas, and ovaries. These observations are consistent with those previously documented in which B[a]P induced injection site tumors and tumors in the abdomen and pancreas of mice injected i.p. (Hecht et al. 1994, Balansky et al. 2006). As there were so few mice observed to have these lesions, no analysis was performed to examine the effect of radiation. "
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    • "The first generation of the cross between C57BL/6J and 129/SvJ strains (B6/129 F1) underwent spontaneous alopecia areata, an inflammatory skin disease, and hair bulb cell apoptosis. This phenotype was greatly accelerated by FHIT heterozygosity, suggesting that FHIT may play a role in the pathogenesis of alopecia areata [40] "
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