Carcinogen Dimethylbenzanthracene Research Articles

Chemical Carcinogen (Dimethyl-benzanthracene) Induced Transplantable Cancer in Fanconi Anemia (Fanca-/-) Mice.

Patients with radiation sensitive Fanconi anemia (FA) are presenting with cancers of the oral cavity, oropharynx, and other anatomic locations. Animal models for cancer in FA mice used orthotopic tumors from wild type mice. We derived a cancer cell line from Fanca-/- mice by topical application of the chemical carcinogen dimethyl benzanthracene (DMBA). A Fanca-/- mouse rhabdomyosarcoma was derived from a Fanca-/- (129/Sv) mouse. The in vitro clonogenic survival of the Fanca-/- clone 6 cancer cell line was consistent with the FA genotype. Transplanted tumors demonstrated hypoxic centers surrounded by senescent cells. This Fanca-/- mouse syngeneic cancer should provide a valuable resource for discovery and development of new normal tissue radioprotectors for patients with FA and cancer.

Thymoquinone Increased Expression of CD4CD25Treg in Sprague-Dawley Rats Induced Dimethylbenzanthracene

BACKGROUND: The carcinogen dimethylbenzanthracene (DMBA) is immunotoxic. Thymoquinone, meanwhile, is known to have antioxidant and anti-inflammatory effects. AIM: This study aims to determine the effect of thymoquinone and tamoxifen on the CD4CD25Treg count in Sprague-Dawley (SD) rats induced by DMBA. METHODS: The 50 SD rats were divided into five groups. Group I (normal control) was given standard drinking and food. Group II was given thymoquinone, Group III was given tamoxifen, Group IV was given DMBA, and Group V was given solvent control. Thymoquinone, tamoxifen, and solvent control administration started 2 weeks before DMBA administration and continued during DMBA induction. In the 3rd week, except for the normal group, all groups were created to be induced with 10 × 20 mg/kg body weight of DMBA for 5 weeks. In the 21st week, surgery and data collection were performed. The hematology profile and CD4CD25Treg number were carried out employing a flow cytometer. The difference in the average number of CD4CD25Treg and blood cells between groups was analyzed with one-way analysis of variance RESULTS: The results revealed that DMBA induction reduced the number of erythrocytes, HB levels, platelet counts, and leukocyte counts (p < 0.05). The administration of thymoquinone and tamoxifen reduced the hematopoiesis effect of DMBA. The thymoquinone and tamoxifen group had a higher number of CD4CD25Treg and leukocytes than the DMBA group (p < 0.05). CONCLUSION: There was no difference in the average CD4CD25Treg, leukocyte count, lymphocyte count, and monocyte count between the thymoquinone and the tamoxifen groups (p > 0.05).

Arsenite and cadmium promote the development of mammary tumors.

Previous studies demonstrate that the heavy metal cadmium and the metalloid arsenite activate estrogen receptor-alpha in breast cancer cells by forming a high-affinity complex with the ligand-binding domain of the receptor and that environmentally relevant doses of cadmium have estrogen-like activity in vivo. The present study showed that in estrogen-receptor positive cells, arsenite and cadmium increased the global expression of estrogen-responsive genes and that an environmentally relevant dose of arsenite also had estrogen-like activity in vivo. Similar to estrogens, exposure of ovariectomized animals to arsenite induced the expression of the progesterone receptor, GREB1, and c-fos in the mammary gland and the expression of complement C3, c-fos, and cyclin D1 in the uterus and the increase was blocked by the antiestrogen ICI-182,780. When virgin female animals were fed a diet, that mimics exposure to either arsenite or cadmium, and challenged with the chemical carcinogen dimethylbenzanthracene, there was an increase in the incidence of mammary tumors and a decrease in the time to tumor onset, but no difference in the total number of tumors, tumor multiplicity, or total tumor volume. Together with published results, these data showed that environmentally relevant amounts of arsenite and cadmium had estrogen-like activity in vivo and promoted mammary tumorigenesis.

The Effect of N-Methyl-N-Nitrosourea (MNU) and Dimethylbenzanthracene (DMBA) in Developing the Mammary Tumor in Wistar Albino and Sprague Dawley Rats-A Comparative Study

The existing methods for the induction of tumor in mammary cancer research using animal models are lengthy, perilous, and sometimes irreproducible and not convenient. Therefore, objective of the study was to find out, a most effective less time consuming model to produce mammary tumor in animal mode. We used two different strains of animals and two carcinogens MNU and DMBA in different concentrations to induce mammary tumor. In this study we found that Sprague Dawley rats developed malignant mammary tumor within two months of time compared to the Wistar strain and size of the tumor increased exponentially. Histopathological examination revealed that the tumors which were induced were showing adenocarcinomas of mammary gland. Therefore, this study suggests that Sprague dawley rats and MNU as carcinogen is the better animal model for tumor induction having least tumor latency and maximum tumor incidence in breast cancer research compared to Wistar albino rats.

Evolution of metastasis revealed by mutational landscapes of chemically induced skin cancers.

Human tumors show a high level of genetic heterogeneity, but the processes that influence the timing and route of metastatic dissemination of the subclones are unknown. Here we have used whole-exome sequencing of 103 matched benign, malignant and metastatic skin tumors from genetically heterogeneous mice to demonstrate that most metastases disseminate synchronously from the primary tumor, supporting parallel rather than linear evolution as the predominant model of metastasis. Shared mutations between primary carcinomas and their matched metastases have the distinct A-to-T signature of the initiating carcinogen dimethylbenzanthracene, but non-shared mutations are primarily G-to-T, a signature associated with oxidative stress. The existence of carcinomas that either did or did not metastasize in the same host animal suggests that there are tumor-intrinsic factors that influence metastatic seeding. We also demonstrate the importance of germline polymorphisms in determining allele-specific mutations, and we identify somatic genetic alterations that are specifically related to initiation of carcinogenesis by Hras or Kras mutations. Mouse tumors that mimic the genetic heterogeneity of human cancers can aid our understanding of the clonal evolution of metastasis and provide a realistic model for the testing of novel therapies.

Whey Protein Hydrolysate but not Whole Whey Protein Protects Against 7,12-Dimethylbenz(a)anthracene-Induced Mammary Tumors in Rats

Effects of intact and processed bovine milk proteins on development of chemically induced mammary tumors in female rats were compared. AIN-93G diets were made with 20% casein (CAS), casein hydrolysate (CASH), intact whey protein (IWP), or whey protein hydrolysate (WPH). Pregnant Sprague-Dawley rats were fed the diets starting at Gestational Day 4. Offspring were fed the same diet. At 50 days, female offspring (44–49/group) were gavaged with sesame oil containing 80 mg/kg of the mammary carcinogen dimethylbenzanthracene (DMBA) and euthanized 62 days posttreatment. Rats fed WPH had an adenocarcinoma incidence of 17% compared to the rats fed CAS, CASH, and IWP diets (34%, 33%, and 36% respectively) (P < 0.001). Median palpable tumor latency for rats fed WPH was greater (61 days, P < 0.001) compared to CAS (44 days), CASH (42 days) and IWP (45 days). Tumor multiplicity was also lower (1.5 vs. 3.0, P < 0.05) in rats fed WPH than in CAS and CASH fed groups. Results demonstrate that hydrolytic processing of whey protein is required for this diet to be effective in reducing DMBA-induced mammary tumors. The bioactive compounds produced during whey protein processing and mechanisms underlying the anticancer effects of WPH are yet to be identified.

P53 prevents progression of nevi to melanoma predominantly through cell cycle regulation

p53 is the central member of a critical tumor suppressor pathway in virtually all tumor types, where it is silenced mainly by missense mutations. In melanoma, p53 predominantly remains wild type, thus its role has been neglected. To study the effect of p53 on melanocyte function and melanomagenesis, we crossed the ‘high-p53’Mdm4+/− mouse to the well-established TP-ras0/+ murine melanoma progression model. After treatment with the carcinogen dimethylbenzanthracene (DMBA), TP-ras0/+ mice on the Mdm4+/− background developed fewer tumors with a delay in the age of onset of melanomas compared to TP-ras0/+ mice. Furthermore, we observed a dramatic decrease in tumor growth, lack of metastasis with increased survival of TP-ras0/+: Mdm4+/− mice. Thus, p53 effectively prevented the conversion of small benign tumors to malignant and metastatic melanoma. p53 activation in cultured primary melanocyte and melanoma cell lines using Nutlin-3, a specific Mdm2 antagonist, supported these findings. Moreover, global gene expression and network analysis of Nutlin-3-treated primary human melanocytes indicated that cell cycle regulation through the p21WAF1/CIP1 signaling network may be the key anti-melanomagenic activity of p53.

Impaired T lymphocyte function increases tumorigenicity and decreases tumor latency in a mouse model of head and neck cancer

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most frequent cancer worldwide. SCC is the most common malignant tumor of the oral cavity with over 35,000 cases and 8,000 deaths reported in the United States each year. Previous case studies have reported increased incidence of HNSCC in patients on immunosuppressive therapy for organ transplantation. The results of these studies indicate that effective immune surveillance is important for preventing emergence of HNSCC. HNSCC may also inhibit immune response to tumor cells, which may be responsible for progression. We previously reported induction of metastatic HNSCC in p53 null mutant mice. Despite induction with the potent carcinogen dimethylbenzanthracene, each mouse developed only 1-2 primary tumors with a relatively long induction period of 22 weeks. We hypothesized that immune surveillance might eliminate early tumor cells resulting in the relatively small number of primary tumors and long induction time. To test this hypothesis we performed the induction protocol in nude mice which have defective T lymphocyte function. Decreased T lymphocyte function resulted in reduced tumor latency and increased tumor formation. Immunohistochemical studies showed that expression of cell cycle regulatory proteins is similar in mouse and human HNSCC. However, distinct differences exist between primary and metastatic tumors from nude and wild-type mice. We also determined that lymphocytes react to metastatic tumor cells by upregulating immunoglobin gene expression but are prone to apoptosis via decreased expression of survival factors and upregulation of cell death genes.

Origin and Development of the Precursor Lesions in Experimental Pancreatic Cancer in Rats

Notwithstanding the importance of understanding how pancreatic ductal adenocarcinoma develops, the process remains controversial. A key question is whether the cells of origin of the tubular complexes that constitute precursor lesions are derived from a single cell type or from multiple types. Suggestions that they arise solely from centroacinar cells or ductal cells have been based on inference due to their morphologic appearance in tissue from patients or investigation of limited numbers of tubular complexes in animal models later in the carcinogenic process. The present study establishes clearly that two steps are involved; rapid transdifferentiation to produce tubular complexes followed later by transformation of the component cells. Animals were killed at intervals beginning 1 day after implantation of the carcinogen dimethylbenzanthracene. Transdifferentiation of acinar cells to ductal cells does not require cell division. Transition of lobules to tubular complexes begins by 2 days after implantation of carcinogen. Within 4 days after implantation well-developed tubular complexes are present. Islets participate in the process. Ductal adenocarcinoma is observed by 1 month after implantation of carcinogen. Chymotrypsin and cytokeratin localized by immunocytochemistry indicate acinar and ductal cell characteristics. Acino-ductal transdifferentiation persists in carcinogen-implanted animals, but not in controls implanted with sodium chloride crystals or subjected to sham implantation. The precursor lesions (tubular complexes) are formed by the transdifferentiation of acinar cells and to a lesser extent islet cells, with the incorporation of the duct cells pre-existing in the lobules. Therefore, cells that at one time were acinar cells, islet cells, and duct cells, provide the precursor cells for the ductal adenocarcinoma that develops from tubular complexes. The results raise the question whether the transdifferentiated cells in the tubular complexes of patients with chronic pancreatitis are more susceptible to carcinogenic influences, resulting in the increased rate of pancreatic cancer.

Aneuploidy Precedes and Segregates with Chemical Carcinogenesis

A century ago, Boveri proposed that cancer is caused by aneuploidy, an abnormal balance of chromosomes, because aneuploidy correlates with cancer and because experimental aneuploidy generates “pathological” phenotypes. Half a century later, when cancers were found to be nonclonal for aneuploidy, but clonal for somatic gene mutations, this hypothesis was abandoned. As a result, aneuploidy is now generally viewed as a consequence, and mutated genes as a cause of cancer. However, we have recently proposed a two-stage mechanism of carcinogenesis that resolves the discrepancy between clonal mutation and nonclonal karyotypes. The proposal is as follows: in stage 1, a carcinogen “initiates” carcinogenesis by generating a preneoplastic aneuploidy; in stage 2, aneuploidy causes asymmetric mitosis because it biases balance-sensitive spindle and chromosomal proteins and alters centrosomes both numerically and structurally (in proportion to the degree of aneuploidy). Therefore, the karyotype of an initiated cell evolves autocatalytically, generating ever-new chromosome combinations, including neoplastic ones. Accordingly, the heterogeneous karyotypes of “clonal” cancers are an inevitable consequence of the karyotypic instability of aneuploid cells. The notorious long latent periods, of months to decades, from carcinogen to carcinogenesis, would reflect the low probability of evolving by chance karyotypes that compete favorably with normal cells, in principle analagous to natural evolution. Here, we have confirmed experimentally five predictions of the aneuploidy hypothesis: (1) the carcinogens dimethylbenzanthracene and cytosine arabinoside induced aneuploidy in a fraction of treated Chinese hamster embryo cells; (2) aneuploidy preceded malignant transformation; (3) transformation of carcinogen-treated cells occurred only months after carcinogen treatment, i.e., autocatalytically; (4) preneoplastic aneuploidy segregated with malignant transformation in vitro and with 14 of 14 tumors in animals; and (5) karyotypes of tumors were heterogeneous. We conclude that, with the carcinogens studied, aneuploidy precedes cancer and is necessary for carcinogenesis.

Use of Primary Rat and Human Hepatocyte Sandwich Cultures for Activation of Indirect Carcinogens: Monitoring of DNA Strand Breaks and Gene Mutations in Co-cultured Cells

Loss of cytochrome P-450 content is a common feature in conventional culture systems of primary hepatocytes. In contrast to the standard in vitro situation, in vivo each hepatocyte is exposed to an extracellular matrix (space of Disse) at two opposing basolateral surfaces. This in vivo symmetry has been reconstructed in vitro by culturing rat or human hepatocytes within two layers of collagen, thus forming a sandwich configuration. Activation of dimethylbenzanthracene (DMBA) or benzo[ a]pyrene (BaP) was studied in rat and human hepatocytes. Genotoxic effects were studied in a three-dimensional co-culture model between sandwich hepatocytes and mammalian cells using the comet assay for detection of DNA strand breaks, and the HPRT test for detection of gene mutations. Sandwich hepatocytes generated active metabolites. The maintenance of metabolic properties in hepatocytes was dependent on extracellular matrix geometry. The number of DMBA- or BaP-induced genotoxic effects tended to be higher than in standard S-9 mix assays. While the ability to activate indirect carcinogens disappears within hours in primary hepatocytes, hepatocyte sandwich cultures enhance their ability to activate indirect carcinogens within 1 wk and retain this activity for up to 2 wk. This is the main advantage of the sandwich method over the more simple and conventional assays. While freshly isolated hepatocytes, regardless of whether in sandwich culture or in conventional assays, are injured by the isolation procedure and possess a corresponding reduced activation ability, hepatocytes in sandwich cultures recover over the course of a few days, and acquire a much higher ability to activate indirect carcinogens. Consequently, the indirect carcinogens BaP and DMBA, which were ineffective (BaP) or exhibited only weak effects (DMBA) at a concentration of 160 nmol/ml in 1–2-day-old hepatocytes, were clearly effective (BaP) or showed about a threefold increase in genotoxicity (DMBA) in 8-day-old hepatocytes in sandwich co-culture. In contrast to the experiments with S-9 mix, which is toxic to mammalian cells and does not allow treatment times of more than 2–3 hr, cells in co-culture with human or rat hepatocytes can be treated for at least 24 hr. The use of sandwich cultures has not yet been described for genotoxicity studies. The results of the present study may perhaps facilitate the acceptance of this method as a co-culture model for the field of genetic toxicology. Use of hepatocytes alone for genotoxicity studies cannot be recommended for difficulties in isolating intact cells from the sandwich cultures. The use of human hepatocytes in sandwich co-culture should enable a more relevant evaluation of potential human genotoxicity with specific chemicals and should put the extrapolation of genetic toxicology data from animal species to humans on a more scientific basis. Beyond that, experiments with animals in vivo could be avoided.

Effect of Curcumin on the Aryl Hydrocarbon Receptor and Cytochrome P450 1A1 in MCF-7 Human Breast Carcinoma Cells

We examined the interaction of curcumin, a dietary constituent and chemopreventive compound, with the carcinogen activation pathway mediated by the aryl hydrocarbon receptor (AhR) in MCF-7 mammary epithelial carcinoma cells. Curcumin caused a rapid accumulation of cytochrome P450 1A1 (CYP1A1) mRNA in a time- and concentration-dependent manner, and CYP1A1 monooxygenase activity increased as measured by ethoxyresorufin- O-deethylation. Curcumin activated the DNA-binding capacity of the AhR for the xenobiotic responsive element of CYP1A1 as measured by the electrophoretic-mobility shift assay (EMSA). Curcumin was able to compete with the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo- p-dioxin for binding to the AhR in isolated MCF-7 cytosol, indicating that it interacts directly with the receptor. Although curcumin could activate the AhR on its own, it partially inhibited the activation of AhR, as measured by EMSA, and partially decreased the accumulation of CYP1A1 mRNA caused by the mammary carcinogen dimethylbenzanthracene (DMBA). Curcumin competitively inhibited CYP1A1 activity in DMBA-treated cells and in microsomes isolated from DMBA-treated cells. Curcumin also inhibited the metabolic activation of DMBA, as measured by the formation of DMBA–DNA adducts, and decreased DMBA-induced cytotoxicity. These results suggest that the chemopreventive effect of curcumin may be due, in part, to its ability to compete with aryl hydrocarbons for both the AhR and CYP1A1. Curcumin may thus be a natural ligand and substrate of the AhR pathway.

Antitumorigenic effect of a mammalian lignan precursor from flaxseed.

Secoisolariciresinol diglycoside (SD), a mammalian lignan precursor found in high-fiber foods, was isolated from flaxseed and tested for effects on mammary tumorigenesis in rats fed a high-fat (20%) diet. Ingestion of purified SD at 1.5 mg/day for 20 weeks starting 1 week after treatment with the carcinogen dimethylbenzanthracene resulted in a 37% reduction (p < 0.05) in the number of tumors per tumor-bearing rat and a 46% reduction (p < 0.05) in the number of tumors per tumor-bearing rat and a 46% reduction (p < 0.05) in the number of tumors per number of rats in each group. Urinary mammalian lignan excretion significantly increased (p < 0.0001) with SD treatment, indicating the conversion of SD to mammalian lignans. No enlargement or gross abnormalities of the major organs were observed in the SD-treated rats. This study showed, for the first time, that SD has an antitumor effect when provided at the early promotion stage of tumorigenesis and may contribute to the health benefits of high-fiber foods.

Acceptance of class II major histocompatibility complex disparate skin grafts associated with suppressor cells and elevated langerhans cell numbers

Class II major histocompatibility complex (MHC) molecules are only present on Langerhans cells (LC) in normal murine epidermis. Depletion of this antigen with the chemical carcinogen dimethylbenzanthracene (DMBA) causes I-E disparate B10.A(2R) congenic tail skin to be accepted permanently when grafted onto B10.A(4R) recipients. Adoptive transfer of spleen cells from these recipients into naive syngeneic hosts inhibited the ability of the host mice to reject untreated B10.A(2R) tail skin grafts. Hence DMBA-treated LC depleted I-E disparate skin grafts activate suppressor cells which did not inhibit BALB/c mice from rejecting a B10.A(2R) tail skin graft. In contrast, the tobacco derived carcinogen benzo(a)pyrene (BP) increased the number of epidermal LC but had no effect on either class I or class II MHC disparate skin graft survival time. This confirms that the number of class II MHC-positive LC is critical for the initiation of skin graft rejection; when the threshold level is attained graft rejection proceeds at a maximal rate that cannot be enhanced by raising the number of LC. The tolerant skin grafts had increased numbers of LC; this was not observed in syngeneic grafts and therefore may be related to the active suppression of immunity.

Microscopic fluorescence in photodynamic therapy

The use of hematoporphyrin derivative (HPD) as a photosensitizer has been studied in malignant tumor detection via fluorescence and in tumor destruction via a toxic photochemical reaction. Squamous cell carcinoma has been induced in hamster buccal mucosa utilizing the known carcinogen dimethyl-benzanthracene. HPD was injected intraperitoneally, then at 24 and 48 hours following injection, unstained frozen section specimens were studied with fluorescent microscopy and photographed. The same specimens were then stained with hematoxylin and eosin and the microscopy correlated. HPD fluorescence was documented in the fibrous stroma of the tumor and in the keratin layer. Essentially no fluorescence was noted in the malignant squamous cells themselves. No consistent differences between the two postinjection times were noted. These qualitative observations support the postulated mechanism of HPD accumulation in tumors.

Natural host defence during oncogenesis. NK activity and dimethylbenzanthracene carcinogenesis.

In this study we determined the effect of administering the chemical carcinogen dimethylbenzanthracene (DMBA) on NK activity mediated by murine splenocytes. The intragastric administration of six weekly 1-mg doses of DMBA to 2- to 3-month-old mice either following a pituitary graft or not, resulted in a tumor incidence which was higher than 60%. The cellularity of the spleens decreased significantly after the third DMBA feeding and the NK activity of these spleens was selectively suppressed. There was no spontaneous reconstitution of the NK activity following cessation of DMBA treatment and during the entire tumor-free period. The adoptive transfer of normal bone marrow, thymus or spleen cells did not restore NK activity in DMBA-treated mice. The NK activity of DMBA-fed mice could be augmented by interferon and by interferon inducers such as poly I:C and dsRNA from Ustilago virus. The effect of these biological response modifiers on NK activity was short-lived but it was possible to restimulate this activity every 24 h. Consecutive treatments of DMBA-fed mice with poly I:C maintained a high level of NK activity for at least 3 weeks.

Increases and perturbations in thymocytes forming spontaneous rosettes during viral and chemical oncogenesis in hamsters

Normal hamster thymocytes were repeatedly observed to form spontaneous (E) rosettes with sheep erythrocytes. The percentage of rosetting thymocytes was subject to reproducible, seasonal variation, fluctuating from consistently high values of up to 17.2% in winter months to <5% in late summer and fall. The number of rosette-forming cells (RFC) increased during the induction of primary, virally, and chemically induced tumorigenesis irrespective of the seasonal variation. Infection of neonate hamsters with SV40 or adenovirus 31 caused significant increases of 50% or more of RFC cells in the thymuses of individual hamsters assayed as early as 2 weeks after infection. Treatment of weanling hamsters with the carcinogen dimethylbenzanthracene (DMBA) produced significant increases in thymocyte RFC at the time of primary tumor appearance. The increases in RFC induced by carcinogenesis appear to be limited to a particular subset of thymocytes defined by assay in dextran compared to a larger population of RFC which could be determined by assay in the presence of heat-inactivated, SRBC-absorbed serum. Induction of primary tumors had the most effect in increasing RFC within the dextran-defined thymocyte subset, as challenge with tumor cells only effected slight RFC increases.

Quantitative histological changes during early experimental carcinogenesis in the hamster cheek pouch.

Sequential changes in the hamster cheek pouch epithelium following application of the carcinogen dimethyl benzanthracene have been assessed using stereological techniques. The most important progressive change found following cessation of carginogen painting appears to be an increase in the number and size of progenitor cells. Much of the marked increase in stratum corneum thickness seen in the early stages appeared to be related to a hyperplasiogenic rather than a neoplasiogenic action of the carcinogen.

Induction of antibodies against carcinogenic polycyclic aromatic hydrocarbons

MANY carcinogens can elicit antibodies when linked to macromolecular carriers1–5. If antibodies against an entire class of carcinogens could be elicited by a non-carcinogenic analogue, and proved capable of neutralising the biological effects of the carcinogens, human immunisation might be of practical value. Mucosal (predominantly IgA) antibodies, capable of facilitating the excretion of an antigen before its absorption into the body, might be particularly useful in this6,7. Here we provide evidence that: an analogue of the polycyclic aromatic hydrocarbon (PAH) carcinogen dim-ethylbenzanthracene (DMBA), substituted with a fluorine moiety to abrogate carcinogenicity, can induce antibodies which bind a variety of PAH carcinogens; that these antibodies can protect tissue culture cells against one of the prominent in vitro biological effects of such carcinogens—toxicity; and that gastrointestinal mucosal immunisation against PAH carcinogens is feasible, and possibly represents a means of achieving in vivo protection by enhancing carcinogen excretion.

Comparative studies on isoaccepting arginyl tRNAs from transformed cells and their utilization in post-translational protein modification

-Comparative studies on the arginine-incorporating activity by the post-translational protein modification system in transformed or infected cells revealed that: (1) Transfer of arginine from arginyl-tRNA was better with the extract obtained from polyoma-infected baby mouse kidney cells than extracts from uninfected controls but similar efficiency of transfer was observed between the extracts of SV40-3T3 and 3T3 cells. Extracts of rat embryo cells transformed by the chemical carcinogen dimethylbenzanthracene, but not by 2-methylcholanthrene, had a higher arginine-incorporating activity than its normal counterpart. (2) On RPC-5 columns, the chromatographic profiles of isoaccepting arginyl-tRNAs derived from transformed or infected cells and their normal counterparts were similar. (3) The transfer of arginine from two species of isoaccepting arginyl-tRNAs of polyoma-infected baby mouse kidney cells was better than that from arginyl-tRNA of uninfected cells.