Differences in serum alpha-fetoprotein concentrations during the carcinogenic sequences resulting from exposure to diethylnitrosamine or acetylaminofluorene.
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2-Acetylaminofluorene↗
Biomedical subjects
F F Becker
Publications and source records attributed to F F Becker.
alpha-Fetoprotein levels and hepatic alterations during chemical carcinogenesis in C57BL/6N mice.
Hepatocellular carcinomas were induced by administration of acetylaminofluorene or chlordane to C57BL/6N mice. Lesions which closely resembled the neoplastic nodule described as a putative premalignant lesion in rats were evident. alpha-Fetoprotein elevations were noted only in the presence of the malignant lesions for both carcinogens. In this regard, the responses of these mice were similar to those seen during spontaneous hepatocarcinogenesis.
2-Acetylaminofluorene↗
Rat alpha-macrofetoprotein (acute-phase alpha 2-macroglobulin) during hepatocarcinogenesis.
Rat alpha-macrofetoprotein (AMF) and alpha-fetoprotein (AFP) are secreted by the fetal liver and become elevated in serum during hepatocarcinogenesis and in animals bearing hepatocellular carcinomas. It has been suggested that these fetal plasma proteins may be influenced by related control mechanisms. The experiments presented herein examined the early responses of these plasma proteins during hepatocarcinogenesis using the hepatocarcinogens acetylaminofluorene and diethylnitrosamine. Under these conditions, AFP serum concentrations were elevated within a few days of exposure to acetylaminofluorene, whereas AMF serum concentrations remained essentially normal. AFP became elevated after a number of weeks of exposure to diethylnitrosamine. In either regimen, AMF became elevated only later when large primary hepatocellular carcinomas were found. The time of appearance of AMF after transfer of an AFP-secreting Morris hepatoma indicated that AMF was elevated only in animals with extremely large, necrotic tumors. Thus, it appears that elevation of serum AFP resulted from either exposure to hepatocarcinogens or production by hepatocellular carcinomas, but that the elevations of serum AMF levels resulted from inflammatory injury or necrosis of tumor tissues.
2-Acetylaminofluorene↗
Activation of endogenous type-C viral p30 antigen in chemically-induced rat hepatocellular carcinomas.
Chemically induced rat hepatocellular carcinomas were prospectively examined for expression of the major group-specific antigen (p 30) of genetically transmitted rat type-C viruses. Ten primary tumors induced following oral administration of the carcinogen N-2-acetylaminofluorine did not express elevated levels of viral antigen as compared to antigen levels detected in normal liver tissue. By contrast, rapidly growing transplantable hepatocellular carcinomas (THCs) derived from primary tumor expressed increased quantities of viral antigen. The expression of antigen was marginally elevated after only one transplanation, increased to maximal levels after several transplant generations and, once achieved, was stably maintained throughout subsequent transplants. Studies with additional previously established THCs showed that poorly differentiated, rapidly proliferating tumors tended to express elevated levels of viral antigen, while more differentiated, slowly growing tumors did not. The results show that the expression of endogenous type-C viral 30 antigen is a stable phenotypic property of many rat THC lines.
2-Acetylaminofluorene↗
Lentigo maligna and lentigo maligna melanoma. Recognition and treatment.
Lentigo maligna is the preinvasive stage of lentigo maligna melanom, which is a specific type of cutaneous malignant melanom found almost exclusively in the head and neck area. The distinguishing features and the biological behavior of this disease are discussed. Emphasis is placed on early diagnosis by clinical differentiation from other pigmented lesions and by biopsy specimen. Treatment by adequate surgical removal with appropriate reconstruction is discussed and illustrated with case reports.
Aged↗
Comparison of transcription stimulating, phenol-soluble non-histone chromosomal proteins in normal rat liver and transplantable hepatocellular carcinomas.
The non-histone chromosomal proteins (NHCP) of a rapidly and slowly proliferating transplantable hepatocellular carcinoma (THC) were compared to those of normal and regenerating rat liver. The total quantity of NHCP is approximately threefold higher in the THCs than in either normal rat liver at 4 h and 44 h regenerating rat liver. Only those NHCP that can be extracted from chromatin by 0.35 M NaCl were further examined and it was observed that the proteins of this highly complex fraction could be further fractionated by their differential phenol-solubility. The phenol-soluble 0.35 NHCP contained protein(s) capable of stimulating the level of DNA-directed RNA synthesis in vitro. The total amount of this stimulatory activity was 5 times higher in the rapidly growing THC and 1.6 times higher in the slowly growing THC than in normal rat liver. In order to assess the contribution of cell-cycle dependent alterations on the increase in the amount of stimulatory activity in the THCs, 44 h regenerating rat livers were examined. This tissue represents a mix of cells in various stages of the cell cycle which is similar to that found in the THCs. It was found that the total quantity of NHCP in the 44 h regenerating rat liver was the same as in normal rat liver. The total amount of the stimulatory activity also was similar in both the normal and 44 h regenerating rat liver. The amount of the stimulatory activity was found to double in 4 h regenerating rat liver, however. These data suggest that the alterations observed in the NHCP of the THCs are not due solely to cell cycle dependent changes, but may represent malignancy dependent alterations.
Animals↗
Reconstruction of facial defects resulting from Mohs' chemosurgical procedures.
A philosophy of reconstruction after removal of cutaneous neoplasms from the face is presented and differences in reconstruction required after Mohs' fixed-tissue and fresh-tissue techniques are discussed. The indications for repair at once or later of facial defects after Mohs' procedures are reviewed and reconstructive alternatives are presented. Illustrative case reports of such cases that have been reconstructed are recounted and commented on. It is likely that the practice of the fresh-tissue technique will stimulate more interest in reconstructing facial defects resulting from that type of operation immediately, or at least sooner than later.
Aged↗
Patterns of spontaneous metastasis of transplantable hepatocellular carcinomas.
A number of transplantable rat hepatocellular carcinomas of varied phenotype were examined for their ability to metastasize. A striking diversity of pattern was observed, ranging from presentation in almost every organ to none at all. No relationship between metastatic capability and growth rate, tumor size, chromosome composition, or other functional characteristics was noted. Interestingly, several of the tumors demonstrated a lymphatic to vascular route of spread, very similar to that of human tumors.
Animals↗
Alteration of the ability of liver microsomes to activate N-2-fluorenylacetamide to a mutagen of Salmonella typhimurium during hepatocarcinogenesis.
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2-Acetylaminofluorene↗
The surgical treatment of nasal skin cancer.
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Basal Cell Carcinoma↗
Normal endonuclease activities for damaged DNA during hepatocarcinogenesis.
Two endonuclease activities in rat liver for damaged DNA were assayed. Double-stranded, covalently closed DNA from phage PM2 was damaged by either ultraviolet irradiation or by heating at acid pH, and used as substrate for endonucleases specific for ultraviolet DNA damage and for DNA apurinic sites, respectively. The levels of both enzyme activities in livers of normal rats were compared to levels in livers of rats fed N-2-acetylaminofluorene. At critical stages of the carcinogenic regimen levels of both endonuclease activities were normal. This, together with other data, suggests that depression of excision-repair of DNA damage does not take place during experimental carcinogenesis.
2-Acetylaminofluorene↗
A comparative study of the nonhistone proteins of rat liver euchromatin and heterochromatin.
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Animals↗
Endogenous DNA polymerase activity in fractionated rat lever chromatin.
Chromatin isolated from adult rat liver was fractionated into template active and inactive components by controlled shearing and glycerol gradient centrifugation. The fractionated chromatin was assayed for DNA-dependent DNA polymerase (DNA mucleotidyl transferase EC 2.7.7.7) activity with and without exogenous activated DNA serving as template. With endogenous chromatin as template, it was found that 90% of the endogenous chromatin bound DNA polymerase activity was located in the transcriptionally active fraction of chromatin, while the distribution of DNA polymerase assayed with exogenous activated DNA was found to be 65% in the transcriptionally active and 35% in the inactive fractions. However, when DNA polymerase was solubilized from these fractions by salt extraction, enzyme activity was found to be equally distributed, suggesting that the difference in endogenous DNA polymerase activity observed between eu- and heterochromatin is due to the restricted template found in repressed fractions.
Animals↗
Local tissue flaps in reconstructive facial plastic surgery.
When a lesion is excised from the facial are and the defect cannot feasibly be closed primarily or by secondary healing, skin grafting or adjacent tissue transfer is usually used to close the defect. In the facial area, adjacent tissue transfer gives a better color and texture match and is preferred over skin grafting whenever possible. This paper presents some local flaps which are available for reconstruction of surgical defects in the facial area.
Face↗
Serum alpha-fetoprotein in a mouse strain (C3H-Avy fB) with spontaneous hepatocellular carcinomas.
In a study of the association between circulating alpha-fetoprotein concentrations and spontaneous hepatocellular carcinomas, we examined C3H-Avy fB mice, which with age consistently demonstrate a rapidly increasing incidence of hepatic cancer. Although elevated alpha-fetoprotein levels are observed in association with the majority of these tumors, no elevation of alpha-fetoprotein was observed during the life course of non-tumor-bearing mice despite their age-dependent risk for hepatic cancer. Therefore, whatever the evolutionary or age-related biological changes may be that lead to tumor formation in this mouse, they are not linked to the synthesis of significant amounts of this oncofetal protein.
Age Factors↗
Chromosome analysis of hepatocellular carcinoma 7777 and correlation with alpha-fetoprotein production.
The Morris hepatocellular carcinoma 7777 is productive of extraordinarily high levels of the oncofetal protein, alpha-fetoprotein. Its chromosome composition was examined in detail since it represents the only near-diploid tumor of such productivity and has been reported to demonstrate a single unusual chromosomal alteration. The major finding is the presence of a submetacentric marker chromosome, composed of a No. 7 chromosome and a short arm that demonstrated a poorly defined banding pattern on Giemsa staining. This marker is unique to 7777 and is of particular interest in view of recent reports of an association between such unbanded chromosome arms and supraproduction of cell products.
Animals↗
Ethanol metabolism by a transplantable hepatocellular carcinoma. Role of microsomes and mitochondria.
1. Ethanol metabolism in slices or homogenates of transplantable hepatocellular carcinoma HC-252 (HC-252) was 50 to 60% of the rate found in host liver slices or homogenates when they were expressed per gram of tissue wet weight and 70 to 80% of the liver when the rates were expressed per milligram of tissue protein. At 10 mM ethanol, the activities of alcohol dehydrogenase in tumor and liver supernatants were comparable. 2. Tumor microsomes did not oxidize ethanol in the presence of a NADPH-generating system, indicating the absence of the microsomal ethanol-oxidizing system and catalase-mediated peroxidation of ethanol. The HC-252 microsomes were contaminated with catalase, and acetaldehyde production occurred in the presence of a H2O2-generating system (xanthine oxidase). The virtual absence of ethanol oxidation and drug metabolism (aminopyrine demethylase and aniline hydroxylase) in HC-252 microsomes may be due to the low activities of NADPH-cytochrome c reductase, NADPH oxidase, and NADPH-dependent oxygen uptake. 3. Microsomal oxidation of ethanol was present in Morris hepatoma 5123C, a well-differentiated tumor of intermediate growth rate, while activity was negligible in microsomes from Morris hepatoma 7288CTC, a less differentiated tumor. Microsomal NADPH oxidase was present in the well differentiated tumor 5123C but was lacking in the less differentiated tumor 7288CTC. Several microsomal, mitochondrial, and cytosolic properties of HC-252 are similar to those of Morris hepatoma 7288CTC but differ from those of the more differentiated 5123C tumor and normal liver. 4. The content of mitochondrial protein in HC-252 was only 25% that of liver, and oxygen consumption per gram of tumor was only 28% that of the liver. When corrected for the mitochondrial protein content, oxygen uptake in tumor HC-252 and liver homogenates was comparable. Isolated tumor and liver mitochondria displayed comparable State 4 and 3 rates of oxygen consumption with succinate and glutamate as substrates. The activities of the reconstituted malate-aspartate and alpha-glycerophosphate shuttles were only slightly lower in isolated HC-252 mitochondria compared to liver mitochondria, when shuttles were reconstituted with purified enzymes. 5. Antimycin inhibited alcohol metabolism,and pyruvate stimulated alcohol metabolism, much less in tumor slices than in liver slices, suggesting the presence of an augmented mitochondria-independent, cytosolic mechanism for oxidizing reducing equivalents in the tumor. These factors suggest that oxidation of NADH is the limiting factor in ethanol metabolism. Whereas, in the liver mitochondrial reoxidation is predominant, in HC-252, cytosolic reoxidation of NADH also plays a major role.
Adenosine Triphosphatases↗