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Influence of FHIT on benzo[a]pyrene-induced tumors and alopecia in mice: Chemoprevention by budesonide and N-acetylcysteine
Authors
BALANSKY R
Carlo Maria CROCE
+7 more
D'AGOSTINI F
DE FLORA S.
DI MARCO B
GANCHEV G
IZZOTTI A
LUBET RA
ZANESI N
Publication date
1 January 2006
Publisher
Doi
Cite
Abstract
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 × 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. © 2006 by The National Academy of Sciences of the USA
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Last time updated on 02/02/2024