Detection of direct mutagenicity of cigarette smoke condensate in mammalian cells.
Mutagenicity of cigarette smoke condensate (CSC) and the acidic, basic and neutral fractions of CSC was examined in the AL hybrid cell, a Chinese hamster ovary cell containing one human chromosome 11. Since the human chromosome 11 is not necessary for survival of the AL cells, mutations involving large deletions and chromosomal loss by non-dysjunction are non-lethal events that are detectable by loss of human cell surface antigens (a1, a2 and a3) encoded by genes on chromosome 11p (a1 and a3) and 11q (a2) through an antibody-complement lysis assay. Exposure of AL cells to CSC without exogenous metabolic activation caused a dose-dependent cytotoxicity and mutagenicity. Mutagenicity also increased with time of incubation up to 3 h with a maximum of 300 a1- mutants/10(5) survivors (250% above background; P less than 0.0005) after incubation with 100 micrograms/ml CSC. Cytotoxicity and mutagenicity of CSC were inversely proportional to cell density. Fifty percent lethal doses for the acidic, basic and neutral fractions of CSC after 3 h of incubation were 30, 100 and 240 micrograms/ml respectively, and the acidic fraction at a concentration of 25 micrograms/ml induced 350 a1- mutants/10(5) survivors (230% above background; P less than 0.0005); the basic and neutral fractions were less mutagenic. These results indicate that CSC and fractions of CSC can directly produce a spectrum of mutations, through both deletional and non-dysjunctional mechanisms of a kind known to lead to inactivation of tumor suppressor genes.
Matsukura
N
N
Laboratory of Human Carcinogenesis, NCI, Bethesda, MD 20892.
Willey
J
J
Miyashita
M
M
Taffe
B
B
Hoffmann
D
D
Waldren
C
C
Puck
T T
TT
Harris
C C
CC
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006822:Hybrid Cells / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D012906:Smoke / Q000009:adverse effects*; D013997:Time Factors
D009153:Mutagens; D012906:Smoke; D008769:Methylnitronitrosoguanidine