Biomedical subjects

W G Hammond

Publications and source records attributed to W G Hammond.

At least 37 records · Page 2Linked to original sources

PubMed1991

Variable regression of experimental bronchial preneoplasia during carcinogenesis.

It has been thought that squamous severe atypical metaplasia of the bronchus is reliably precancerous. The canine subcutaneous bronchial autograft model for studying the progression of epidermoid carcinogenesis (normal----regular squamous metaplasia----mild, moderate, and severe atypical metaplasia----squamous cell carcinoma) provides evidence that severe atypical metaplasia of the bronchial epithelium is reversible. Among 148 subcutaneous bronchial autografts that had serial sampling of the epithelium and exposure to implants of methylcholanthrene, severe atypical metaplasia was noted in 28 that received only a single implant. During the total carcinogen exposure (median 24.5 months), 9 of 28 (32%) developed squamous cell cancer, and 19 of 28 (68%) regressed toward normal. Severe atypical metaplasia was noted in 34 subcutaneous bronchial autografts that received two or more carcinogen implants: epidermoid cancer developed in 26 of 34 (76.5%), and regression toward or to normal occurred in 8 of 34 (23.5%). Severe atypical metaplasia was not detected in 53 subcutaneous bronchial autografts: 19 that received only a single implant and 34 that received two or more implants. Progression and regression occurred among these subcutaneous bronchial autografts in proportions similar to those found in subcutaneous bronchial autografts wherein severe atypical metaplasia was seen. Among 33 subcutaneous bronchial autografts initially studied after 6 months of exposure to carcinogen, progression to severe atypical metaplasia was seen 3 months later in 19 of 33 that had additional exposure; in the same interval regression of epithelial abnormalities occurred in 14 of 33 subcutaneous bronchial autografts that had no additional exposure (p less than 0.05). We have presented evidence that severe atypical metaplasia includes at least three cell populations: one committed to cancer without further stimulus, one that regresses despite further carcinogen exposure, and one that requires additional carcinogen to progress to cancer. At least in this model, severe atypical metaplasia is not inexorably precancerous. The subcutaneous bronchial autograft model is suitable for seeking biologic indicators of irreversibility.

Animals↗

PubMed1990

Bronchiolo-alveolar regions in adenocarcinoma arising from canine segmental bronchus.

Adenocarcinomas induced in canine bronchial segments placed subcutaneously have bronchiolo-alveolar regions. Immunocytochemistry and routine staining of adjacent sections strongly suggests that the lining of these regions consists of type II cells. These regions may thus represent true prospective alveolar regions, as also seen in embryonic lungs. This first observation of bronchoalveolar cancer arising from a major bronchus indicates that the carcinogen-induced neoplastic progression in bronchial epithelium may lead to type II cell differentiation and type II cell tumor development. The preservation of cell properties in serial nude mouse transplants suggests that it is a stable type II cell population.

Adenocarcinoma↗

PubMed1990

Effects of 5-azacytidine in Syrian golden hamsters: toxicity, tumorigenicity, and differential modulation of bronchial carcinogenesis.

5-Azacytidine (AZC) was studied in a lung cancer model in outbred and syngeneic (F1D) hamsters wherein benzol[a]pyrene (BP) from sustained release implants (SRI) induces preneoplastic mucosal changes which progress to bronchogenic cancer. In pilot studies to evaluate AZC toxicity, a dose schedule of 5 mg/kg biweekly was found suitable and was then used for long-term administration in all subsequent studies. Three groups of outbred hamsters were studied: BP SRi alone (n = 60), BP SRI + AZC (n = 60), and AZC alone (n = 54). AZC treatment was begun 3-5 days after SRI placement. Sixty-one days after the start of the experiment, seven or eight hamsters were sacrificed from each group. Later sacrifices were at 3-week intervals in groups receiving BP SRI and at 6-week intervals in the AZC only group. Four groups of F1D syngeneic hamsters were studied: BP SRI alone (n = 50); BP + AZC starting 3-5 days after SRI placement and continuing until death (n = 52); BP + AZC from 3 to 5 days until 75 days after SRI placement (n = 49); BP + AZC starting 80 days after SRI placement and continuing until death (n = 52). Hamsters (n = 9-14) from each group were sacrificed at 120, 150, 180, and 220 days after SRI implantation. AZC alone was not carcinogenic under these conditions. Both outbred and F1D hamsters treated with early or continuous AZC had slower rates of neoplastic change from BP SRI than did animals receiving BP SRIs alone or BP + late AZC. The incidence of epidermoid cancer were the same for all regimens, but the tumors in those receiving AZC early in carcinogenesis were smaller than in those receiving late or no AZC. The incidences of nonepidermoid cancer were lower in those receiving AZC during early carcinogenesis, and larger tumors were noted in the absence of AZC. Thus, within the study period in this unique hamster lung cancer model, AZC given early in carcinogenesis inhibited only the later (promotional) phase of BP epidermoid carcinogenesis, but inhibited all phases of nonsquamous cancer development induced by BP. This differential modulation of bronchial carcinogenesis, which occurs from AZC given during preneoplastic stages, may prove useful for delineating molecular mechanisms underlying specific phenotypic types of bronchogenic cancers.

Animals↗

PubMed1990

Automated computerized rat eater meter: description and application.

A real-time Automated Computerized Rat Eater Meter was developed by modifying commercially available metabolic cages. Food access via a feeding tunnel was monitored by photocells. Food consumption was measured by an electronic scale. The signals thus generated were processed by a computer. This allowed us to continuously measure the spontaneous feeding behavior of free-feeding nondeprived Fischer rats for a sum total of 35 study days. Based on our data, we defined a meal as an episode of food consumption preceded and followed by at least 5 minutes of no feeding. Fischer rats showed periodic nychthemeral eating behavior. Food consumption, number of meals, meal sniffs, intermeal sniffs, and, consequently, eating activity were greater during the dark cycle than the light cycle. Meal duration, meal size, and thus food consumption rates remained constant throughout both cycles. Our modification of commercially available metabolic cages provides unique data for continuously monitoring rat feeding patterns over prolonged periods of time.

Animals↗

PubMed1990

Nutritional support in surgical practice: Part I.

Critical evaluation of the therapeutic benefit gained from provision of nutritional support requires knowledge regarding the nutritional status of those to whom it was given. The apparent effect of giving parenteral nutrition or enteral nutrition depends not only on how much and how well it is given, but also on how depleted the recipient is. Thus, nutritional assessment requires close examination before proceeding to assess the efficacy and potential benefits of the remedial measures of parenteral nutrition or enteral nutrition. Although preoperative malnutrition is associated with a poor operative outcome, there appears to be no consensus as to whether perioperative nutritional support can reduce postoperative complications to the level occurring in well-nourished patients undergoing similar procedures. This is partly because reports evaluating the effect of perioperative nutritional support on postoperative outcome vary widely as to numbers of patients studied, primary diagnoses, and the duration and quality of perioperative nutritional support. In Part I, these issues are explored in patients who are undergoing operations for cancer, trauma, or burns. Enteral nutrition appears to be as effective as parenteral nutrition in improving operative outcome, as compared with ad libitum oral nutrition. Postoperative enteral nutrition and parenteral nutrition are equally effective in reducing postoperative complications.

Enteral Nutrition↗

PubMed1990

Nutritional support in surgical practice: Part II.

On admission, a group of high-risk patients who are potential candidates for surgery can be identified, in whom prompt initiation of preoperative enteral or parenteral nutrition may reduce postoperative morbidity and mortality irrespective of the nutritional status. Among these are patients with inflammatory bowel disease, gastrointestinal fistulas, and pancreatitis. Substantial nutritional support has little or no direct effect upon the pathogenesis of the disease, but the discontinuance of oral intake may well have a beneficial effect on the basic disease process. Thus, the provision of enteral or parenteral nutrition gives the patient an optimal opportunity to marshal host defenses in support of healing. In organ system failures, e.g., acute renal failure, liver failure, and pulmonary failure, appropriate nutritional support may assist the patient in coping with the abnormal intermediary metabolism resulting from such failure until satisfactory organ system function returns. From this review, it seems reasonably clear that the initially malnourished patient is less able to successfully withstand the adverse effects of vigorous therapy and/or severe illness than is the well-nourished individual. Hence, correction of malnutrition, either before initiating therapy or concomitant with the treatment, is very likely to be beneficial.

Acute Disease↗

PubMed1990

Quantitative DNA alterations during 5-azacytidine-induced differential modulation of benzo(a)pyrene carcinogenesis in hamster bronchi.

Sustained release implants (SRI) containing 10% benzo(a)pyrene (BP) were placed endobronchially into outbred and syngeneic (F1D) hamsters. Randomly selected OB and F1D hamsters also received 5-azacytidine (AZC), 5 mg/kg i.p., twice weekly until death (AZC-CONT); two more groups of F1D hamsters were given the same AZC dose either for the first 75 days of SRI implantation (AZC-EARLY) or from 80 days after SRI placement until death (AZC-LATE). OB Hamsters were sacrificed at regular intervals from 62 to 189 days of SRI exposure. F1D Hamsters were sacrificed in groups after 120, 150, 180, and 220 days of SRI exposure. The bronchial mucosa at the SRI site was examined cytologically and histologically, as were the tumors that developed. Mean quantitative total cellular DNA values (QDNA) were measured by image analysis. For both varieties of hamster given AZC, QDNA values were higher in early carcinogenesis (CG) and lower in the late stage of CG than in hamsters that did not get AZC (P less than 0.001). QDNA values were lower in epidermoid than in non-epidermoid cancers (P less than 0.001); for both types of cancer, QDNA was lower in AZC-treated hamsters (P less than 0.01). Cancers induced under the influence of AZC included more epidermoid cancers (P less than 0.01) and were of a higher degree of differentiation (P less than 0.01) than those induced by BP alone, especially when AZC was given early in CG. There was no consistent relationship between QDNA and degree of differentiation in tumors. These differential effects of AZC given early during CG suggest that 1) for epidermoid bronchial CG, some of the molecular alterations involved in hyperploidy and in differentiation occur early in the sequential progression of carcinogenesis; and 2) for both epidermoid and non-epidermoid bronchial CG, the necessary changes must occur in a fixed sequence instead of as random events, until all needed changes have occurred.

Animals↗

PubMed1988

Non-small cell lung cancer in autogenous subcutaneous bronchial grafts in dogs.

The progression of preneoplasia into lung cancer can be serially studied in a new canine model that is simpler and more cost effective than previously reported methods of orthotopic endobronchial carcinogenesis. Short segments of bronchus, obtained by pneumonectomy, were placed on the back of 10 dogs in the form of subcutaneous bronchial autografts. These autografts (12 to 14 per dog) became vascularized and lined with normal respiratory epithelium. Four to 12 weeks after autograft implantation, 10% methylcholanthrene in crystalline form was put into 57 autografts and 10% methylcholanthrene in a silicone polymer sustained-release implant was placed into 54 autografts. Ten autografts without carcinogen (one per dog) served as controls. Serial samplings of each autograft during 9 to 97 weeks of carcinogen exposure showed the neoplastic progression from normal bronchial cells to invasive cancer through stages such as atypical squamous metaplasia and carcinoma in situ. To date, cancers have been histologically proved in 60 autografts; 36 were induced by implants and 24 by the crystalline form. Thirty-nine cancers were epidermoid, and the remainder were either adenocarcinomas (n = 3) or poorly differentiated spindle cell cancers (n = 18). The sustained-release implant method resulted in larger autografts with a greater tendency to progress to cancer than the crystalline carcinogens (p greater than 0.025). Therefore, the sustained-release implant is now considered the preferred method. Measurement of nuclear deoxyribonucleic acid by image analysis of nine histologic cancers demonstrated hyperploidy. Deoxyribonucleic acid from the L1 repeated sequence family was demonstrably hypomethylated in spindle cell tumors. Curettement of individual autografts yielded sheets of respiratory epithelium from which 43.5 to 409.5 micrograms of deoxyribonucleic acid was isolated. For the first time, deoxyribonucleic acid from each stage of the neoplastic progression in non-small cell lung cancer is available in adequate quantities for serial biochemical and therapeutic analysis.

Animals↗

PubMed1988

Biochemical and cytogenetic studies of human lung cancers.

In ongoing studies, we have tested resected lung cancers from 41 men and 49 women; of those with primary lung cancer, 46 patients are free of disease and 35 have died of cancer or have persistent disease. Measurements and studies were as follows: total cellular deoxyribonucleic acid content by image analysis (n = 77); total genomic deoxyribonucleic acid methylation state and banding patterns from probed Southern blots (n = 36); radioimmunoassay for motilin, bombesin, gastrin, vasoactive intestinal peptide, and cholecystokinin (n = 18); and cytogenetic analysis (n = 39). All lung cancers were hyperploid. Adenocarcinomas and epidermoid carcinomas were generally hexaploid to nearly septaploid; comparisons by stage and histologic features suggested potential prognostic correlations. There was general hypomethylation of deoxyribonucleic acid (p less than 0.001). Deoxyribonucleic acid digests from restriction endonuclease Hpa II, when probed with deoxyribonucleic acid homologous to KPN, showed banding patterns that separated histologically indistinguishable primary adenocarcinomas and metastatic adenocarcinomas from one another. Cancers studied with radioimmunoassay were all negative for polypeptide hormones. Five cancers grew adequately in vitro to permit study of 190 detailed karyotypes (20 to 50 per tumor). Chromosome modal numbers ranged from 49 to 109. There were from 4 to 20 clearly abnormal marker chromosomes per tumor; abnormality derived from chromosome 1 was prevalent. Ten of 19 tumors xenotransplanted to nude mice were carried through two to five transplant generations without a change in histologic patterns.

Animals↗

PubMed1987

Differential susceptibility to bronchial carcinogenesis in syngeneic hamsters.

Previous studies of chemical carcinogenesis in the lung of Syrian golden hamsters have utilized outbred (nonsyngeneic) animals. Using the endobronchial sustained release implant technique, which causes focally originating cancers in outbred hamsters, we studied the course of bronchial carcinogenesis in two varieties of syngeneic Syrian golden hamsters, the LSH and the F1D strains (BIO 15.16 male X BIO 87.20 female). With either 10% benzo(a)pyrene or 10% methylcholanthrene sustained release implants the time course of epithelial transition from normal to neoplastic was the same for F1D hamsters as previously described for outbred hamsters. Using 10% benzo(a)pyrene sustained release implants the incidence of cancers as a function of time was significantly lower (P less than 0.001) in LSH hamsters as compared to outbred and F1D animals. Of 19 tumors transplanted into syngeneic F1D hamsters, 16 have been successfully propagated by serial transplantation. We conclude that (a) F1D hamsters are comparable to outbred animals in the response of their bronchial epithelium to endobronchial benzo(a)pyrene and methylcholanthrene, (b) there are significant differences in susceptibility to bronchial chemical carcinogenesis among hamster strains, thereby giving opportunity to study potential genetic control mechanisms during bronchial carcinogenesis, and (c) F1D hamsters are suitable for studies of lung cancer biology using tumor transplantation methods.

Animals↗

PubMed1986

Use of 20% fat emulsion in total parenteral nutrition.

Sixteen elderly postoperative patients were randomized in a crossover study comparing isocaloric volumes of 20% and 10% fat emulsions used for total parenteral nutrition (TPN). The caloric intake was maintained constant during the two 7-day periods of each infusion. The indices measured after each period were total volume of fluid administered, change in body weight, hematocrit, serum sodium, creatinine, albumin, blood urea nitrogen, glucose, inorganic phosphate, and cholesterol. The total volume of 10% isocaloric nutrient solution was significantly (p less than .05) greater than that of the 20% solution. A rise in body weight and a fall in serum indices of hydration status were observed; five patients developed clinical signs of overhydration while on the 10% solution. These changes did not occur with the 20% solution. Thus, isocaloric substitution of a 20% fat emulsion for a 10% fat emulsion with TPN prevented overhydration and hemodilution without compromising nutrient intake.

Aged↗

PubMed1986

Differential interaction of normal and preneoplastic hamster bronchi with adriamycin.

Advanced bronchogenic carcinoma in humans is notoriously resistant to the cytocidal actions of cancer chemotherapy. The experiments reported here were undertaken as a first step in examining the mechanisms of resistance of carcinogen-altered bronchus to the actions of the commonly used cancerocidal agent Adriamycin. Syrian Golden hamsters were treated with an endobronchial carcinogen in order to produce bronchial neoplasms or with no carcinogen as controls. Hamsters were then given i.v. Adriamycin, and the amounts and metabolism of bronchial Adriamycin were determined. Peak uptake values were found 5 min after Adriamycin administration, and the amounts of Adriamycin in normal and carcinogen-altered bronchi were found to be similar. Whereas no metabolism of Adriamycin was observed in normal bronchi, 40-60% of total Adriamycin fluorescence was found to be due to Adriamycinol and Adriamycin aglycones in bronchi with premalignant changes. In separate experiments, the susceptibility of normal and carcinogen-altered bronchial extracts to drug-induced lipid peroxidation was measured in vitro. A 50% decrease was found in the ability of carcinogen-altered bronchi to act as a substrate for lipid peroxidation mediated by Adriamycin and an approximately 30% decrease for lipid peroxidation induced by t-butyl-hydroperoxide. These results demonstrate two different mechanisms by which bronchogenic carcinomas might become resistant to the chemotherapeutic actions of Adriamycin. These are by the carcinogen induction of metabolism of Adriamycin to less toxic products and by resistance of the bronchi to free radical damage.

Animals↗

PubMed1986

Carcinogenesis in heterotopic respiratory epithelium in canine subcutaneous bronchial autografts.

Short bronchial segments obtained by pneumonectomy were implanted, 9-12 per dog, in the subcutaneous tissues of the back of seven dogs. These subcutaneous bronchial autografts (SBA) became vascularized, and they contained viable, histologically normal respiratory epithelium 4 wk after implantation. From 1-3 mo after implantation, 10% methylcholanthrene in steroid suspension medium was instilled into 21 SBAs, and 10% methylcholanthrene in a silicone polymer sustained release implant was placed in 22 SBAs. Ten SBAs were left carcinogen free as controls. SBA contents were examined cytologically at 3-mo intervals. Biopsies were done from 2-32 mo after carcinogen implantation. Progressive preneoplastic changes were noted in all five dogs which received carcinogen. Curetments of five SBAs after 14-mo exposure to methylcholanthrene yielded 10(4)-10(5) cells from each SBA; 40-70% of the cells obtained were at the same stage of atypical squamous metaplasia. At least one SBA in each dog yielded cancer cells by cytological criteria by 19-29 mo after instillation. Biopsy of a grossly abnormal SBA revealed well-differentiated epidermoid carcinoma at 32 mo. The multiple SBA method provides isolated portions of canine respiratory epithelium for the study of chemical carcinogenesis and for the production of sizable preneoplastic cell populations.

Animals↗

PubMed1986

Endobronchial carcinogenesis in dogs.

A canine model of squamous cell lung cancer has been developed through studies with 110 dogs exposed by 11 focal endobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benzo(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high-dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five T1-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine carcinomas of lesser stages. The following regimens caused cancers: sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; benzo(a)pyrene and topical nitrosomethylurea; low-dose dimethylbenzanthracene; high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methylcholanthrene given by submucosal injection every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has followed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive cancer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean total cellular deoxyribonucleic acid content from diploid in normal cells to greater than tetraploid in cancer cells (p less than 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.

Adenocarcinoma↗

PubMed1985

Aspects of amino acid and protein metabolism in cancer-bearing states.

Overt malnutrition is seen in about 40% of patients hospitalized for treatment of cancer. In patients whose primary treatment modality is surgical, morbidity and mortality is twice as high in the malnourished group as in the normally nourished patients. This clinically important malnutrition is a consequence of obligatory parasitism by the tumor, which grows at its own genetically determined rate and which competes effectively with the host for the limited available nutrients. Administration of extra nutritional support as total parenteral nutrition (TPN) can alter the tumor-host nutritional balance so that host repletion may occur. Provision of a significant proportion of TPN calories as fat diminishes the incidence of glucose intolerance and reduces the incidence of abnormal liver function. In vitro and in vivo studies both show that leucine is the significant controlling branched-chain amino acid in the TPN mixture, and adequate leucine content is a crucial component of effective TPN. Variations in TPN content of large neutral amino acids have important effects on brain tyrosine and tryptophan availability and hence may also effect neurotransmitter activity. Although the usefulness of TPN for correcting malnutrition in cancer patients is clear, the optimal choices of constituents for the TPN mixture continue to evolve.

Adenosine Triphosphate↗

PubMed1984

Amelioration of metabolic complications of conventional total parenteral nutrition. A prospective randomized study.

The most common metabolic complications of total parenteral nutrition (TPN), glucose intolerance and abnormal liver function, can be significantly reduced when 30% of the glucose calories are replaced by fat. We gave 88 patients either conventional TPN (CON-TPN, 25% dextrose and 4.25% amino acids) or modified TPN (MOD-TPN, 15% dextrose, fat, and 5% amino acids). The treatment groups were as follows: group A, no surgery with TPN only; group B, postoperative TPN; and group C, preoperative and postoperative TPN. Serial blood samples were analyzed for glucose, albumin, triglycerides, and insulin, and for liver function values. Nine patients manifested hyperglycemia and were removed from the study; seven patients had received CON-TPN and two had received MOD-TPN. In group A, the insulin level rose 50% less with MOD-TPN. There was a 50% smaller rise in the triglyceride, SGOT, and SGPT levels in patients who received MOD-TPN. Replacing one third of the TPN glucose calories with fat leads to better glucose tolerance and fewer hepatic complications.

Female↗

PubMed1984

Carcinogenesis in canine bistomal heterotopic tracheal grafts.

Successful canine lung cancer models have required repeated focal bronchial carcinogen exposure under general anesthesia. To simplify serial studies of the respiratory mucosa during carcinogenesis, bistomal autologous heterotopic tracheal pedicle grafts have been made. These grafts can readily be returned to the original orthotopic site, and this has been shown to be a method with which to study reversibility of mucosal changes. Polycyclic aromatic hydrocarbons were applied topically to the mucosa three times a week for 21 to 22 months in 21 grafts. Implants of Silastic polymer from which carcinogen was released in sustained-release fashion were then left in the grafts for 4 to 6 weeks. Serial cytological and histological examinations showed development of atypical squamous metaplasia in the graft mucosa. Mucosal papillomatosis was noted in 4 of 7 grafts surgically excised 17 to 18 months after completion of carcinogen exposure. The heterotopic bistomal tracheal graft provides a useful method for studying respiratory epithelial carcinogenesis without repeated general anesthesia.

Animals↗

PubMed1984

A family of epidermoid lung cancer models.

A method of sustained release implantation has been developed whereby Silastic cylinders, impregnated with benzo[alpha]pyrene (BP) or methylcholanthrene (MCA) each at 2% (low dose) and 10% (high dose) concentrations, were inserted into the bronchus intermedius of hamsters. High-dose BP and MCA, and low-dose MCA had first-order exponential release rates: the half-time of release was 40 days for high-dose BP, 30 days for high-dose MCA, and 165 days for low-dose MCA. Release rate of low-dose BP was a second-order function: half-time of release was 40 days. Atypical squamous metaplasia was noted by 4 weeks in more than 65% of hamsters after insertion of each high-dose carcinogen but in less than 30% with the low-dose carcinogens. Carcinoma in situ was noted approximately 8 weeks after high-dose BP and 19 weeks after low-dose BP. At about 15 to 17 weeks after a high-dose carcinogen, 64% of animals had invasive epidermoid cancer, whereas after a low-dose carcinogen, only 21% did. After 25 weeks of exposure to a high-dose carcinogen, more than 85% of hamsters had invasive epidermoid cancer; up to 52 weeks were required for invasive epidermoid cancer to develop in 30% after a low-dose carcinogen. Measured by image analysis, nuclear deoxyribonucleic acid content of cells with severe atypical squamous metaplasia was greater than tetraploid (mean +/- standard deviation [SD], 3.77 +/- 1.4), whereas cells with invasive epidermoid cancer were suprahexaploid (mean +/- SD, 6.48 +/- 3.6). These differences are significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗