Fernandez A, Mondal S, Heidelberger C
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7272-6. doi: 10.1073/pnas.77.12.7272.
When C3H/10T1/2 cells are treated with a given concentration of a chemical carcinogen, the transformation frequency can vary over 4 orders of magnitude, depending primarily upon the number of cells plated. To explain this phenomenon, we have developed a probabilistic theory of the formation of transformed foci in this system. We define p1 as the probability that a cell will be activated by carcinogen treatment, p2 as the probability per cell generation that an activated cell will be transformed, and p3 as the probability per cell generation that an activated cell will be deactivated. The equation we have derived: log (F/N) = log [2p1p2(1 -- p3)/2(1 -- p3) -- 1]+ n log (1 -- p3) describes focus formation; F is mean number of loci per dish after carcinogen treatment, N is number of cells in a dish at confluence, and n is number of cell generations to confluence. This equation has been verified experimentally; p3 = 0.24 and p1p2 = 3.8 X 10(-6) at a single concentration of 3-methylcholanthrene. This relationship explains previously inexplicable effects of cell density on transformation frequency.
当用给定浓度的化学致癌物处理C3H/10T1/2细胞时，转化频率可在4个数量级范围内变化，这主要取决于接种的细胞数量。为了解释这一现象，我们在此系统中建立了一个关于转化灶形成的概率理论。我们将p1定义为细胞被致癌物处理激活的概率，p2定义为每个细胞世代中被激活的细胞发生转化的概率，p3定义为每个细胞世代中被激活的细胞失活的概率。我们推导的方程：log (F/N) = log [2p1p2(1 - p3)/2(1 - p3) - 1] + n log (1 - p3)描述了灶形成情况；F是致癌物处理后每个培养皿中灶的平均数，N是汇合时培养皿中的细胞数，n是达到汇合的细胞世代数。这个方程已通过实验验证；在3-甲基胆蒽的单一浓度下，p3 = 0.24且p1p2 = 3.8×10(-6)。这种关系解释了以前无法解释的细胞密度对转化频率的影响。
