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PubMed1976

Histogenesis and growth pattern of 1,2-dimethylhydrazine-induced rat colon adenocarcinoma.

The histogenesis and growth pattern of colon adenocarcinoma have been studied using 74 BD IX rats given 20 mg 1,2-dimethylhydrazine hydrochloride per kg, s.c., weekly from Day 11 to their 24th week and serially sacrificed with controls. Modifications in DNA synthesis activity and early tumor changes were sought on histological and radioautographic preparations of normal-appearing colon mucosa. All visible colorectal tumors were analyzed for size, site, and pathology. Chronic dimethylhydrazine treatments resulted in a simultaneous increase in the number of both total and tritiated thymidine-labeled cells in the glands of Lieberkühn. In addition, microscopic carcinomatous foci were observed after the 15th week, and the first macroscopic adenocarcinomas appeared in 24-week-old animals. Their number thereafter exponentially increased with time. A total of 252 macroscopic tumors were obtained, of which 14 were classified as signet ring cell carcinomas and 238 as adenocarcinomas. Among the latter, local invasion could be documented in 230, including the smallest. No benign polypcancer sequence could be demonstrated in this material. The average growth pattern of those adenocarcinomas could be adequately described by a Gompertz curve, with a short initial doubling time (e.g., 7.5 days in 1.0-cu mm tumors) that progressively increases with time (e.g., 59.6 days in 5000-cu mm tumors).

Adenocarcinoma↗
PubMed1986

Effects of differing purified cellulose, pectin, and hemicellulose fiber diets on fecal enzymes in 1,2-dimethylhydrazine-induced rat colon carcinogenesis.

The fecal microflora enzymes, beta-glucuronidase and beta-glucosidase, as well as fecal bacterial counts, were examined during colon carcinogenesis in rats administered parenteral 1,2-dimethylhydrazine and fed nutritionally equivalent diets free of fiber or containing one of three single sources of dietary fiber (cellulose, hemicellulose, and pectin). Whereas pectin-fed animals had increased fecal beta-glucuronidase activities, those fed cellulose and hemicellulose, two fibers protective in dimethylhydrazine colon neoplasia, had decreased activities. Although fecal bacterial counts were not significantly changed, similar differential changes in fecal beta-glucosidase activity were noted: cellulose but not pectin or hemicellulose feeding was associated with reduced activity. Although cellulose fiber may cause differing physiological effects resulting in a reduction in colonic neoplasia development in this experimental animal model, decreased bacterial metabolic enzyme activation of carcinogens or cocarcinogens may lead to diminished exposure of colonic cells to exogenous or endogenous mutagens.

Animals↗
PubMed1979

Protective effect of oral Salmonella enteritidis 11RX infection against colon tumor induction by 1,2-dimethylhydrazine in mice.

Infection of mice with Salmonella enteritidis 11RX has been shown previously to cause nonspecific immune stimulation and, consequently, resistance to subsequent challenge with a variety of transplantable tumors. The present study has examined the effect of infection with this organism in a chemical carcinogenesis system. Colonic tumors were induced in LACA and BALB/c x C57BL/6JF1 mice by weekly s.c. injection of 1,2-dimethylhydrazine (15 mg/kg) for 28 weeks. Infection of mice p.o. with live S. enteritidis 11RX at 8-week intervals during 1,2-dimethylhydrazine administration protected both strains against colon tumorigenesis. Significantly fewer infected than control BALB/c x C57BL/6JF1 mice had colonic tumors at or before termination of the experiment (34 or 40 weeks) (p less than 0.001 in all cases). Comparable results were obtained with both male and female mice. The difference in tumor incidence between control and infected LACA mice was not statistically significant, however; the number and size of the lesions was greater in control mice (p less than 0.02). Although it has not been proven that the protective effect is mediated by the immune system, the results are consistent with the operation of a macrophage-mediated surveillance system. It is suggested that enteric infections should be considered as a possible contributing factor in the epidemiology of human colonic cancer.

Adenocarcinoma↗
PubMed1984

Enhancement of 1,2-dimethylhydrazine-induced rectal carcinogenesis following chronic ethanol consumption in the rat.

The incidence, distribution, size, and histopathology of grossly visible intestinal tumors induced by the parenteral administration of 1,2-dimethylhydrazine dihydrochloride were examined in 32 paired rats fed a nutritionally adequate liquid diet containing 36% of total calories either as ethanol or isocaloric carbohydrates. The liquid diets were begun 4 wk before the first of four weekly injections of 1,2-dimethylhydrazine dihydrochloride. At the time of the subcutaneous application of the procarcinogen, liquid diets were omitted for 3 wk, and were replaced by a standard laboratory diet. This feeding schedule was repeated four times, and after 32 wk the animals were killed. Chronic ethanol ingestion increased the total number of rectal tumors significantly (17 vs. 6, p less than 0.02). However, alcohol had no effect on tumor size or histopathology. Chronic ethanol ingestion did not exhibit any cocarcinogenic effect in tissues other than the rectum. A 47% increase in the activity of mucosal alcohol dehydrogenase in the distal colorectum was found between chronically ethanol-fed rats and pair-fed controls (0.241 +/- 0.019 vs. 0.164 +/- 0.020 mumol X mg protein-1 X h-1, p less than 0.01). This could in part explain the cocarcinogenic effect of alcohol in this tissue. Fecal bile acids, however, do not play a role as promoters of rectal cancer under the present experimental conditions. The data give experimental support to the epidemiologic findings of an increased incidence of rectal cancer in the alcoholic.

Adenocarcinoma↗
PubMed1978

DNA alkylation in mice with genetically different susceptibility to 1,2-dimethylhydrazine-induced colon carcinogenesis.

The formation and persistence of methylated purines was determined in mice that received a single s.c. injection of 1,2-[14C]dimethylhydrazine (15 mg/kg) and were allowed to survive for 12 or 60 hr. In mice with a low susceptibility to dimethylhydrazine-induced colon carcinogenesis (C57BL/Ha), concentrations of 7-methylguanine and O6-methylguanine in DNA of colon, ileum, and kidney were 40 to 60% less than in mice with a high incidence of colonic tumors (ICR/Ha). In hepatic DNA the extent of methylation was higher in C57BL/Ha than in ICR/Ha mice. The rate of loss of methylated purines from colon DNA was similar in both strains. In all organs investigated the metabolic incorporation of 14C into normal DNA bases was lower in C57BL/Ha than in ICR/Ha mice. It is concluded that the low carcinogenic response of C57BL/Ha mice is due to the smaller extent of initial alkylation of colon DNA, which probably reflects differences in the enzymic metabolism of the parent carcinogen.

Animals↗
PubMed1978

Effects of diet on colon carcinogenesis and the immune system in rats treated with 1,2-dimethylhydrazine.

The effects of different types of diets on colon carcinogenesis by 1,2-dimethylhydrazine and on the immune system were studied in W/Fu rats. Six different types of diets were used in two sets of experiments. Rats in each group were fed the respective diets immediately upon weaning. 1,2-Dimethylhydrazine dihydrochloride was administered s.c. at a dosage of 15 mg/kg weekly in two divided doses. The rats were followed by sequential laparotomies for the development of gastrointestinal (GI) tumors until death. Tumors appeared earlier, and the total number of GI tumors, particularly those of the colon, was higher in rats fed diet enriched with fat from animal sources. In these rats the GI tumors metastasized more frequently, and their survival, after appearance of the first GI tumor, was significantly shortened. The diet low in animal fat and enriched with carbohydrate reduced the number of GI tumors and delayed their appearance. Semisynthetic elemental diet accelerated the appearance of colon tumors without increasing the total number of GI tumors over the life span of the animals. Serum cholesterol levels evaluated during carcinogenesis suggest a correlation between serum cholesterol levels and the increased frequency of colonic tumors. The alterations in serum immunoglobulin G levels, lymphocyte counts, and surface immunoglobulin-bearing lymphocytes evaluated at different times during carcinogenesis suggested a biphasic ("M type") immune response. Rats fed low residue diets and/or diets containing fat from animal sources had depressed serum immunoglobulin G levels. However, the pattern of immune response was similar in groups of rats fed different types of diets.

Animals↗
PubMed1982

[Changes in induced cell loss in the intestinal epithelium of mice after a single exposure to 1,2-dimethylhydrazine].

A single subcutaneous injection of 1,2-dimethylhydrazine lowers the induced cell loss from the superficial regions of mucosa in the distal colon of mice which may be revealed on the 3rd day after injection to retain longer than a month. The magnitude of this effect in the different regions of intestine is closely related to the frequency of tumor appearance established under numerous carcinogen injections. Non-carcinogenous analogs of 1,2-dimethylhydrazine and different carcinogens that induce tumors in other organs, but not in intestine, do not lead to the lowering in the induced cell loss. The data obtained indicate that the above effect may be related to carcinogenous properties of 1,2-dimethylhydrasine.

Animals↗
PubMed1980

Effect of dietary vitamin E on dimethylhydrazine-induced colonic tumors in mice.

This study investigates the effect of variations in dietary vitamin E on the incidence of dimethylhydrazine-induced colonic tumors in mice. Two groups of 65 LACA mice were given 28 weekly s.c. injections of dimethylhydrazine. The only difference in the management of the two groups was the dietary content of vitamin E; one group received 10 mg/kg, and the other group received 600 mg/kg. Of these two groups, 42 and 51 mice, respectively, survived, and there were significantly more adenomas, more adenomas with pleomorphic cytology, and more invasive carcinomas in the group receiving a low vitamin E supplement to their diet. It is suggested that vitamin E may have some part to play in the multifactorial effect of diet on colorectal carcinogenesis.

Animals↗
PubMed1977

Surface changes in the descending colon of rats treated with dimethylhydrazine.

Male Sprague-Dawley rats were given weekly s.c. injections of 1,2-dimethylhydrazine (21 mg/kg) for period of up to 20 weeks. The descending colon of treated animals killed at 2 weekly intervals was examined for morphological change, over a 30-week period, after commencement of treatment using scanning electron microscopy, light microscopy, transmission electron microscopy, and freeze-fracture techniques. Scanning electron microscopy showed that 1,2-dimethylhydrazine treatment resulted in the progressive replacement of the normal arrangement of epithelial cells covering the luminal surface of intestinal glands with enlarged and irregularly shaped arrangements of epithelial cells, so that the entire mucosa was atypical and disorganized at 30 weeks after commencement of treatment. The changes were not readily observable using other methods of microscopy. Multiple tumors that were apparently unrelated to sites of specific morphological change erupted into the intestinal lumen through the atypical epithelium. Tumor surface cells and normal absorptive cells were compared using scanning electron microscopy and transmission electron microscopy of thin sections and freeze-fracture replicas. The results showed that tumor cells were usually smaller, more rounded, showed less regularly shaped microvilli, and had fewer particles in the apical surface membrane than on normal absorptive cells.

Animals↗
PubMed2003

Mechanism of formation of hydrogen trioxide (HOOOH) in the ozonation of 1,2-diphenylhydrazine and 1,2-dimethylhydrazine: an experimental and theoretical investigation.

Low-temperature (-78 degrees C) ozonation of 1,2-diphenylhydrazine in various oxygen bases as solvents (acetone-d(6), methyl acetate, tert-butyl methyl ether) produced hydrogen trioxide (HOOOH), 1,2-diphenyldiazene, 1,2-diphenyldiazene-N-oxide, and hydrogen peroxide. Ozonation of 1,2-dimethylhydrazine produced besides HOOOH, 1,2-dimethyldiazene, 1,2-dimethyldiazene-N-oxide and hydrogen peroxide, also formic acid and nitromethane. Kinetic and activation parameters for the decomposition of the HOOOH produced in this way, and identified by (1)H, (2)H, and (17)O NMR spectroscopy, are in agreement with our previous proposal that water participates in this reaction as a bifunctional catalyst in a polar decomposition process to produce water and singlet oxygen (O(2), (1)delta(g)). The possibility that hydrogen peroxide is, besides water, also involved in the decomposition of hydrogen trioxide is also considered. The half-life of HOOOH at room temperature (20 degrees C) is 16 +/- 1 min in all solvents investigated. Using a variety of DFT methods (restricted, broken-symmetry unrestricted, self-interaction corrected) in connection with the B3LYP functional, a stepwise mechanism involving the hydrotrioxyl (HOOO(*)) radical is proposed for the ozonation of hydrazines (RNHNHR, R = H, Ph, Me) that involves the abstraction of the N-hydrogen atom by ozone to form a radical pair, RNNHR(*) (*)OOOH. The hydrotrioxyl radical can then either abstract the remaining N(H) hydrogen atom from the RNNHR(*) radical to form the corresponding diazene (RN=NR), or recombines with RNNHR(*) in a solvent cage to form the hydrotrioxide, RN(OOOH)NHR. The decomposition of these very labile hydrotrioxides involves the homolytic scission of the RO-OOH bond with subsequent "in cage" formation of the diazene-N-oxide and hydrogen peroxide. Although 1,2-diphenyldiazene is unreactive toward ozone under conditions investigated, 1,2-dimethyldiazene reacts with relative ease to yield 1,2-dimethyldiazene-N-oxide and singlet oxygen (O(2), (1)delta(g)). The subsequent reaction sequence between these two components to yield nitromethane as the final product is discussed. The formation of formic acid and nitromethane in the ozonolysis of 1,2-dimethylhydrazine is explained as being due to the abstraction of a methyl H atom of the CH(3)NNHCH(3)(*) radical by HOOO(*) in the solvent cage. The possible mechanism of the reaction of the initially formed formaldehyde methylhydrazone (and HOOOH) with ozone/oxygen mixtures to produce formic acid and nitromethane is also discussed.

Journal Article↗
PubMed1973

Evaluation of dimethylhydrazine induced tumours in mice as a model system for colorectal cancer.

The evolution and structure of adenomatous polyps and adenocarcinomata of the colon in NMRI mice induced by dimethylhydrazine are described. Severe toxic reactions in the liver and other organs are produced by dimethylhydrazine (DMH), but tumours are induced only in the colon and around the anus. The 100% incidence and growth characteristics of the tumours make it potentially a good model system, but investigators should take into account the widespread nonspecific cellular injury induced by this carcinogen.

Adenocarcinoma↗
PubMed1980

Use of a GC concentrator to improve analysis of low levels of airborne hydrazine and unsymmetrical dimethylhydrazine.

New findings from animal studies indicate that there is a serious cancer risk associated with exposures to hydrazines. In June, 1978, NIOSH announced more restrictive occupational exposure levels for these compounds. Adherence to these limits requires improved analytical methodology. This paper describes a modified method for monitoring hydrazine and unsymmetrical dimethylhydrazine in atmospheric samples below the ceiling concentrations recommended by NIOSH. The method utilizes a GC concentrator for which a "trap" (ventable GC precolumn) was prepared and tested. Using this trap, up to 40 microL sample injections (injections much too large for conventional GC work) are effectively chromatographed. Presented are data on the overall efficiency of the method for airborne hydrazine and unsymmetrical dimethylhydrazine in the concentration ranges of 0.02 - 0.67 mg/m3 and 0.04 - 1.04 mg/m3, respectively.

Air Pollutants↗
PubMed1996

Primary monoclonal and secondary polyclonal growth of colon neoplastic lesions in C3H/HeN<-->BALB/c chimeric mice treated with 1,2-dimethylhydrazine immunohistochemical detection of C3H strain-specific antigen and simple sequence length polymorphism analysis of DNA.

To determine the clonality and cellular origin of colon pre-neoplastic and neoplastic lesions, C3H/HeN<-->BALB/c chimeric mice treated with 1,2-dimethylhydrazine (DMH) were investigated immunohistochemically using a specific antibody to C3H strain-specific antigen (CSA) enabling immunohistochemical discrimination of C3H cells in histological sections of chimeric mouse tissues. To confirm the results of immunostaining, simple sequence length polymorphism (SSLP) analysis was performed on DNA samples extracted from histological sections of adenocarcinomas. C3H/HeN<-->BALB/c chimeric mice were produced by an aggregation procedure and together with BALB/c and C3H/HeN animals were given weekly s.c. injections of 20 mg/kg body weight DMH for up to 20 weeks. At weeks 20 and 35 animals were killed and autopsied. In normal colonic mucosa of the chimeras, each gland was composed entirely of either CSA-positive or -negative cells and no mixed glands were found. Cells of all focal atypias in chimeric mice were, in each case, homogeneous for one or another of the parental types. Of 91 adenomas in chimeric mice, only one comprised both types of cell. Among 119 adenocarcinomas, 12 contained cells of both parental types. In these tumors, however, the 2 phenotypes were not mixed together at random but arranged in discrete areas, with intermingling limited to the junctions. SSLP analysis demonstrated DNAs extracted from CSA-positive and -negative tumors to exhibit the polymorphic patterns of C3H and BALB/c, respectively, while mixed CSA-positive and -negative tumors showed mixtures of both polymorphic DNA types.

1,2-Dimethylhydrazine↗
PubMed1981

Potentiation of dimethylhydrazine bowel carcinogenesis in rats.

An animal model of organ-specific chemical carcinogenesis has been used to study environmental effects on the incidence of human colorectal adenocarcinoma. Wistar/Furth weanling rats underwent connection of their urinary and fecal streams (ureterosigmoidostomy), connection of their urinary and fecal streams with proximal fecal diversion (rectal bladder), or sham operations. Age-matched, unoperated control and operated animals then received either no carcinogen, 1,2-dimethylhydrazine (DMH) 20 mg/kg body weight, s.c. once weekly for 16 weeks, N-[4-(5-nitro-2-furyl)-2-thiazolylformamide (FANFT) 0.2% of the feed for 16 weeks, or DMH + FANFT concurrently. Thirty-three weeks after carcinogen exposure, surviving animals were killed and examined for bowel and urinary bladder tumors. The incidence of adenocarcinoma of the colon adjacent to the junction between bladder and bowel was significantly higher in animals after ureterosigmoidostomy compared with animals whose fecal stream had been proximally diverted (14/22 vs. 0/34, P less than 0.001). This effect was not dependent upon chemical carcinogen exposure. Nonexposed animals still developed a significantly higher incidence of colon adenocarcinomas adjacent to their bladder-bowel junctions as compared with animals with proximal fecal diversion (5/8 vs. 0/13, P less than 0.01). In unoperated or sham operated animals, adenocarcinomas of the bowel occurred in 33% of DMH-treated animals and transitional cell carcinomas of the urinary bladder in 33% of the FANFT-treated animals. After concurrent exposure to both carcinogens, no increased incidence of bladder tumors was noted when compared with FANFT treatment alone. However, the number of animals with one or more adenocarcinomas of the bowel (22/30 vs. 17/50, P less than 0.001), the mean number of tumors per animal (2.1 +/- 0.2 vs. 1.1 +/- 0.1, P less than 0.01), and the invasiveness of the tumors were all increased after DMH + FANFT as compared with DMH exposure alone. The carcinogenic potential of direct bladder to bowel connection with intact fecal and urinary streams, and the potentiation by FANFT of DMH-induced colon carcinogenesis may have implications in the genesis of human colorectal cancer.

1,2-Dimethylhydrazine↗
PubMed1985

Steroid receptors in dimethylhydrazine-induced colon carcinogenesis.

To investigate whether gonadal hormones are involved in the tumorigenesis of dimethylhydrazine (DMH)-induced colonic neoplasms, the authors measured steroid receptors in the neoplasms. 30- or 60-day-old BD-IX rats were injected with 20 mg of 1,2-DMH per kg of body weight once a week for 20 weeks. Fifty-seven rats were sacrificed at 40 to 45 weeks after the initial injection. Androgen receptor (AR), estrogen receptor (ER), and progesterone receptor (PR) were measured in colonic neoplasms. The total number of colonic neoplasms was 274 among 57 rats, 65.8% in male rats and 34.2% in female rats. The mean number of colonic neoplasms per rat was higher in male rats, i.e., 5.6, compared with 3.5 in female rats. A slightly higher number of colonic neoplasms per rat was seen in the rats that had the initial injection at 30 days of age. The number of large colonic neoplasms with a diameter of more than 1 cm was 77 (28.1%), 74% of which were seen in male rats. Thus, a higher incidence of tumors that were also larger were seen in male rats. Histologic findings showed that 53.6% of the neoplasms were carcinomas. The highest incidence of colonic neoplasms was in the distal colon in both sexes. Most of the well-differentiated adenocarcinoma were seen in the distal colon (82.2%), whereas mucinous carcinoma and undifferentiated adenocarcinoma were prominent in the proximal colon or cecum (56.1%). In rats with a normal colon, low levels of AR and PR were determined; but ER was not found in any regions of the colon. In DMH-induced colonic cancer, the incidence as well as the concentration was higher in male rats (60.6%, 16.9 +/- 3.6 fm/mg protein), compared with female rats (40.0%, 4.6 +/- 0.8 fm/mg protein). Similar incidences and levels of ER and PR were seen in both sexes. There was no relationship between steroid receptors and histologic findings in colonic neoplasms. These results suggest that the gonadal hormones, especially androgens, appear to be involved in DMH-induced colon tumorigenesis in male rats.

1,2-Dimethylhydrazine↗
PubMed1988

Susceptibility to 1,2-dimethylhydrazine-induced colonic tumors and epithelial cell proliferation characteristics of F1, F2, and reciprocal backcrosses derived from SWR/J and AKR/J parental mouse strains.

Hybrid crosses were performed between SWR/J, a strain highly sensitive to 1,2-dimethylhydrazine (DMH), and AKR/J, a strain highly resistant to the carcinogen. F1 and F2 and reciprocal backcrosses were tested to determine if proliferative characteristics such as high activity, wide compartment (PC), and a large S-phase population in the middle third of crypts were linked to susceptibility and inherited as a dominant autosomal trait as was reported for DMH tumor response. A blend of resistant and sensitive tumor and proliferative characteristics was observed in the F1 and F2 crosses. A tumor incidence of 43.7% in the F1 and 52% in the F2 was obtained rather than the respective 100% and 75% expected frequencies. One week after the sixth injection of DMH, the incidence of focal areas of atypism (FAA) in the backcross to resistance (BCR) and the backcross to sensitivity (BCS) was the same (4.1 per FAA-bearing animal). This suggested that the response to the carcinogen was similar in both groups up to this point. Yet 20 weeks later, the BCR had a 7.3% tumor incidence, far lower than the 50% incidence expected. The BCS had an incidence of 98.6%, not unlike SWR frequencies and close to the expected 100% tumor incidence. Proliferative characteristics in the backcrosses, however, did not revert to parental levels. Instead, the labeling index (LI) or percentage of S-phase cells to total cells scored was significantly higher in the BCR than in the BCS (10.2% +/- 3.2% versus 8.1% +/- 2.2%, P less than 0.02). This study has shown that in crosses between these two strains (SWR/J and AKR/J), susceptibility to DMH-induced tumor is not inherited as a dominant trait. Neither are the proliferative characteristics of the colonic mucosa inherited in a simple Mendelian manner nor are the kinetic properties of the epithelial cells linked to DMH tumor susceptibility. It is suggested that the parental AKR/J strain may contribute a protective or resistant factor, that is, a repressor gene, which impedes the progression of carcinogen-induced foci of dysplasia to colonic neoplasia.

1,2-Dimethylhydrazine↗
PubMed1988

Use of polar solvents in chemoprevention of 1,2-dimethylhydrazine-induced colon cancer.

To examine the effect of the polar solvents on 1,2-dimethylhydrazine (DMH)-induced colon cancer, 100 male Sprague-Dawley rats were randomly allocated to a control and three treatment groups. Treated animals received N-methylformamide (NMF), dimethylsulfoxide (DMSO), or methylsulfonylmethane (MSM) added to drinking water 1 week before carcinogen injections commenced and for the duration of the experiment. Primary tumors were detected by serial laparotomy under ether anesthesia performed at 2-month intervals and commencing after carcinogen injections had been completed. The average time to tumor onset was significantly delayed in rats receiving NMF and MSM (P = 0.0141 and 0.0398 respectively, Mantel-Haenszel test). In addition, fewer poorly differentiated tumors were noted in treatment groups. No weight loss or toxicity was observed. These findings demonstrate that the polar solvents significantly reduce the latent period to tumor onset in DMH-induced colon cancer and indicate the need to further investigate such compounds as chemopreventive agents.

1,2-Dimethylhydrazine↗
PubMed1990

The effect of endotoxin on 1,2-dimethylhydrazine-induced colonic tumors in rats.

The effect of endotoxin on colon tumors was studied in male Sprague-Dawley rats. Colon tumors were induced in weanling rats by the administration of 20 weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH). When colon tumors were detected by colonoscopy in 80% of the rats around week 24 after DMH injection, the animals were divided randomly into two groups. One group served as the control. The other group received six endotoxin (Escherichia coli) treatments every fifth day. The first dose was 50 micrograms/100 g (intraperitoneally); the remaining doses were 100 micrograms/100 g (subcutaneously). Rats were killed 2 weeks after the last endotoxin injection. Endotoxin treatments resulted in larger colon tumors. The median tumor size was 71 mm2 for endotoxin-treated and 31 mm2 for untreated rats (P less than 0.02). Endotoxin treatments also resulted in a significantly higher incidence (P less than 0.05) of ulcer development in the small intestine, that is 47% in the endotoxin-treated versus 23% in the untreated rats. After a single subcutaneous injection of endotoxin (100 micrograms/100 g), the colon mucosal reduced glutathione (GSH) level was raised by 21% at 16 hours, reached a peak on day 2, then decreased to baseline by day 4. The increased GSH level in the colon mucosa was maintained up to the third endotoxin injection. By the fifth injection, no increase in the GSH level was observed. These results suggest that the growth of colon tumors in rats induced by DMH could be enhanced by endotoxin treatments. The enhanced tumor growth may be due to an increase in the colon GSH level and/or other mediators released by macrophages as a result of endotoxin treatments.

1,2-Dimethylhydrazine↗