Site-specific modulation of carcinogen-induced gastrointestinal tract nuclear anomalies in B6C3F1 mice by chloroform.
Chloroform (CHCl3) is an established rodent carcinogen and a prevalent contaminant of chlorine-disinfected drinking water. Thus in the United States CHCl3, along with other trihalomethanes, is regulated not to exceed 100 ppb in potable water. Recently, several studies have shown that CHCl3 also has anti-cancer properties as it inhibits tumor growth in mouse liver and in the gastrointestinal tract of the rat. In this paper we show that CHCl3 also inhibits the propensity for three gastrointestinal tract carcinogens, benzo(a)pyrene (BAP), 1,2-dimethylhydrazine (DMH) and methylnitrosourea (MNU), to induce nuclear anomalies in the proximal colon of the B6C3F1 mouse. For example, in mice pre-adapted to 1800 ppm CHCl3 for 30 days prior to the carcinogen administration the level of nuclear anomalies induced in the proximal colon by BAP was reduced by four-fold (0.9 +/- 0.7 v. 3.6 +/- 1.0 anomalies/10 crypts; p less than 0.001) and two-fold for MNU (2.4 +/- 1.0 v. 4.6 +/- 1.6; p less than 0.001) and DMH (0.9 +/- 0.9 v. 1.7 +/- 0.8; p = 0.03). In the duodenum CHCl3 was effective at inhibiting unclear anomalies only for MNU (45.3 +/- 4.6 v. 30.4 +/- 3.5; p = 0.02). The inhibitory effect of CHCl3 does not extend to nuclear anomalies of the forestomach. The anti-cancer properties of CHCl3 are discussed in light of its cancer causing potential and possible application to human risk assessment.
Daniel
F B
FB
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, OH 45268.
Reddy
T V
TV
Stober
J A
JA
Olson
G R
GR
D019813:1,2-Dimethylhydrazine; D000818:Animals; D000970:Antineoplastic Agents; D001564:Benzo(a)pyrene / Q000633:toxicity; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure*; D002725:Chloroform / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D004127:Dimethylhydrazines / Q000627:therapeutic use; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008815:Mice, Inbred Strains; D009130:Muscle, Smooth / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D013270:Stomach / Q000187:drug effects / Q000473:pathology*
D000970:Antineoplastic Agents; D002273:Carcinogens; D004127:Dimethylhydrazines; D001564:Benzo(a)pyrene; D008770:Methylnitrosourea; D002725:Chloroform; D019813:1,2-Dimethylhydrazine