Conservation of histone carcinogen adducts during replication: Implications for long-term molecular dosimetry

The effect of cell replication on histone-carcinogen adducts was investigated by determining the specific adduct levels as a function of time following carcinogen treatment of human TK6 cells grown in culture. Core histones isolated from cells treated with aflatoxin B1 or r-7,t-8 dihydroxy-t-9,t-10-...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-11, Vol.54 (21), p.5599-5601
Main Authors: ÖZBAL, C. C, VELIC, I, SOOHOO, C. K, SKIPPER, P. L, TANNENBAUM, S. R
Format: Article
Language:English
Subjects:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - analysis
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - metabolism
Aflatoxin B1 - analysis
Aflatoxin B1 - metabolism
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - analysis
Carcinogens - metabolism
Cell Division
Cell Line
Chemical agents
Histones - analysis
Histones - metabolism
Humans
Medical sciences
Methylnitrosourea - analysis
Methylnitrosourea - metabolism
Time Factors
Tumors
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Summary:The effect of cell replication on histone-carcinogen adducts was investigated by determining the specific adduct levels as a function of time following carcinogen treatment of human TK6 cells grown in culture. Core histones isolated from cells treated with aflatoxin B1 or r-7,t-8 dihydroxy-t-9,t-10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene exhibited a decrease over five generations in specific adduct level that did not exceed the decrease expected as a result of dilution with newly synthesized protein except during the early phase (< 1 generation) of the experiment when loss of chemically unstable adducts might occur. Similar kinetics without the initial, more rapid phase was observed when cells were treated with N-nitroso-N-methylurea. Multigeneration stability of aflatoxin B1 and N-nitroso-N-methylurea adducts that formed on histone H1 was also observed; in these experiments it was not possible to determine if there was an initial phase in the kinetics. These experiments indicate that cell replication does not result in the repair or removal of adducted histones, establishing the feasibility of using histone-carcinogen adducts for molecular dosimetry purposes.
ISSN:0008-5472
1538-7445