Gastric carcinogenesis: A model for the identification of risk factors

Biologically Motivated Cancer Risk Models

“…For example, it has been shown that inhibitors of cell proliferation can diminish the risk that chemical carcinogens will induce gastric cancer. (14) If inhibition of mitosis were the single effect of the agent, it would follow that Mo(x, t ) < Mo(O, t ) or M , ( x , t ) < M,(O, t), which would also reduce the background cancer rate. Agents that reduce risk via these mechanisms will be referred to as inhibitors.…”

“…To obtain unique estimates, the following variables are defined: M is the background net transition rate, S is the smallest of the transition rates, and I is the difference or incremental change between the smallest and largest transition rates. Using these definitions, the quadratic equation describing mutation can be expressed as (14) If the tumor rates are observed up to a fixed point in time, t , it follows that the probability that a tumor will develop by time t may be expressed as (15) where V, an estimable combination of parameters, equals C,M[(exp(Gt -1 -G t ) ] / G 2 . Three specific cases of this model, shown in Table 111, will be considered.…”

Dietary Factors ModulateHelicobacter-associated Gastric Cancer in Rodent Models

“…Because of the purported role of high nitrate diets and subsequent nitrosamine formation in the stomach, numerous studies have been conducted in rodents administering various nitrosamines known to be potent carcinogens. In experiments with rats dosed with MNNG, NaCl was shown to have a promotional effect of induction of gastric adenocarcinoma when salt is given intragastrically weekly or in the diet during 12–20 weeks exposure to MNNG in drinking water (Newberne et al ., 1987, Takahashi et al ., 1983, Tatematsu et al ., 1975). It is also known that salt causes damage to rat gastric surface epithelium followed by proliferation of gastric epithelium (Charnley and Tannenbaum, 1985, Furihata et al ., 1984, Ohgaki et al ., 1989, Sorbye et al ., 1988).…”

Helicobacter species and in vivo models of gastrointestinal cancer

“…In experiments with rats dosed with MNNG, NaCl was shown to have a promotional effect of induction of gastric adenocarcinoma when salt is given intragastrically weekly or in the diet during 12-20 weeks exposure to MNNG in drinking water ( Figure 4). [99][100][101] It is also known that salt causes damage to rat gastric surface epithelium followed by proliferation of gastric epithelium. 10,102-104 MNNG and NaC1 ingestion in rats induced up to 100-fold increases of ornithine decarboxylase (ODC) activity and about a 10-fold increase in DNA synthesis in the pyloric region of the stomach.…”