In vitro protective effects of chemopreventive agents against bleomycin-induced genotoxicity in lymphoblastoid cell lines and peripheral blood lymphocytes of head and neck cancer patients.
The protective effects of ascorbic acid (AA), n-acetyl-l-cysteine (NAC), alpha-tocopherol acid (ATA), alpha-tocopherol-acid succinate (TAS), and 13-cis-retinoic acid (CRA) on mutagen-induced chromosomal breakage were studied. Mutagen-sensitivity was determined by the bleomycin assay in human lymphoblastoid cell lines (LCLs) and cultures of peripheral blood lymphocytes (PBLs) from head and neck cancer patients. Preincubation with chemopreventive agents statistically significantly decreased mutagen-induced chromatid breakage in LCLs and PBLs in a dose-related manner. As the concentration of the agents was increased in tenfold increments in the study range, mean breakage rates were reduced by 3.0 to 7.7% in LCLs and by 6.0 to 11.1% in PBLs. The effective concentrations are comparable to those achieved in clinical applications and found in human dietary studies. A similar phenomenon in vivo, if identified, may explain the differences in occurrence of head and neck and other cancers between populations with different dietary habits. The bleomycin assay may be used for studying compounds with presumed chemopreventive properties.
Trizna
Z
Z
University of Texas M. D. Anderson Cancer Center, Department of Medical Oncology, Houston 77030.
Schantz
S P
SP
Lee
J J
JJ
Spitz
M R
MR
Goepfert
H
H
Hsu
T C
TC
Hong
W K
WK
D000111:Acetylcysteine / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D001761:Bleomycin / Q000009:adverse effects*; D002460:Cell Line / Q000187:drug effects; D002869:Chromosome Aberrations; D006258:Head and Neck Neoplasms / Q000097:blood*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000648:ultrastructure; D014212:Tretinoin / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D016587:Antimutagenic Agents; D001761:Bleomycin; D014810:Vitamin E; D014212:Tretinoin; D001205:Ascorbic Acid; D000111:Acetylcysteine