Abstract
A theoretical model of twostage carcinogenesis has been hypothesized. Variables that are modeled include the populations of normal, initiated, and transformed cells; mitotic rates of these cells; hyperplasia; and the probabilities of cell initiation and transformation during replication. The size of the cell populations can be estimated and mitotic rates determined directly from animal studies. Tumor occurrences at different time intervals following varying periods of N[4(5nitro2furyl)2thiazolyl]formamide (FANFT) and sodium saccharin administration are known and are used in the indirect estimation of values for unobservable model variables. Modelbased analyses suggest FANFT markedly increases the probability of cell initiation in addition to its experimentally verifiable effects on increasing the stem cell population and mitotic rates. Further, experimental results appear inconsistent with the hypothesis that FANFT increases the probability of cell transformation over background levels. Similarly, the effect of sodium saccharin was found to be attributable entirely to increases in stem cell populations and mitotic rates without influencing either the probability of initiation or the probability of transformation.
Original language  English (US) 

Pages (fromto)  437445 
Number of pages  9 
Journal  Carcinogenesis 
Volume  5 
Issue number  4 
DOIs 

State  Published  Apr 1 1984 
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ASJC Scopus subject areas
 Cancer Research
Cite this
A general probabilistic model of carcinogenesis : Analysis of experimental urinary bladder cancer. / Greenfield, R. E.; Ellwein, L. B.; Cohen, Samuel Monroe.
In: Carcinogenesis, Vol. 5, No. 4, 01.04.1984, p. 437445.Research output: Contribution to journal › Comment/debate
}
TY  JOUR
T1  A general probabilistic model of carcinogenesis
T2  Analysis of experimental urinary bladder cancer
AU  Greenfield, R. E.
AU  Ellwein, L. B.
AU  Cohen, Samuel Monroe
PY  1984/4/1
Y1  1984/4/1
N2  A theoretical model of twostage carcinogenesis has been hypothesized. Variables that are modeled include the populations of normal, initiated, and transformed cells; mitotic rates of these cells; hyperplasia; and the probabilities of cell initiation and transformation during replication. The size of the cell populations can be estimated and mitotic rates determined directly from animal studies. Tumor occurrences at different time intervals following varying periods of N[4(5nitro2furyl)2thiazolyl]formamide (FANFT) and sodium saccharin administration are known and are used in the indirect estimation of values for unobservable model variables. Modelbased analyses suggest FANFT markedly increases the probability of cell initiation in addition to its experimentally verifiable effects on increasing the stem cell population and mitotic rates. Further, experimental results appear inconsistent with the hypothesis that FANFT increases the probability of cell transformation over background levels. Similarly, the effect of sodium saccharin was found to be attributable entirely to increases in stem cell populations and mitotic rates without influencing either the probability of initiation or the probability of transformation.
AB  A theoretical model of twostage carcinogenesis has been hypothesized. Variables that are modeled include the populations of normal, initiated, and transformed cells; mitotic rates of these cells; hyperplasia; and the probabilities of cell initiation and transformation during replication. The size of the cell populations can be estimated and mitotic rates determined directly from animal studies. Tumor occurrences at different time intervals following varying periods of N[4(5nitro2furyl)2thiazolyl]formamide (FANFT) and sodium saccharin administration are known and are used in the indirect estimation of values for unobservable model variables. Modelbased analyses suggest FANFT markedly increases the probability of cell initiation in addition to its experimentally verifiable effects on increasing the stem cell population and mitotic rates. Further, experimental results appear inconsistent with the hypothesis that FANFT increases the probability of cell transformation over background levels. Similarly, the effect of sodium saccharin was found to be attributable entirely to increases in stem cell populations and mitotic rates without influencing either the probability of initiation or the probability of transformation.
UR  http://www.scopus.com/inward/record.url?scp=0021254049&partnerID=8YFLogxK
UR  http://www.scopus.com/inward/citedby.url?scp=0021254049&partnerID=8YFLogxK
U2  10.1093/carcin/5.4.437
DO  10.1093/carcin/5.4.437
M3  Comment/debate
C2  6705147
AN  SCOPUS:0021254049
VL  5
SP  437
EP  445
JO  Carcinogenesis
JF  Carcinogenesis
SN  01433334
IS  4
ER 