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O H Iversen

Publications and source records attributed to O H Iversen.

At least 19 recordsLinked to original sources
PubMed1991

Circadian variation in cell proliferation and maturation. A hypothesis for the growth regulation of the rat corneal epithelium.

The rat corneal epithelium has been chosen as a model for studying growth regulation. In this epithelium a large single cohort of cells enters the S phase during a fairly short time period once a day. The factor responsible for this wave of cell proliferation is unknown, but it may be a chemical signal from the central nervous system (the suprachiasmatic nucleus or the corpus pineale). The mature cell compartment of the corneal epithelium is assumed to produce a negative feedback factor (chalone), counteracting the effect of the circadian proliferative factor on the local cell proliferation. When no circadian factor is being produced, during most of the 24 h, the chalone seems to enhance the maturation process. During diminished chalone production (e.g. after cell injury and subsequent regeneration), we will get a more or less unrestricted cell proliferation in the tissue with a delayed maturation process prolonging the chalone depletion. This interaction between the circadian proliferative factor and the negative feedback factor for regulation of proliferation with its accompanying stimulatory effect on maturation, may represent a general mechanism in the regulation of cell proliferation in any tissue. Since in at least some organs virtually all cells entering the S phase do this as a single wave once a day, this mechanism may be enough to explain the regulation of cell proliferation during both normal and regenerative conditions.

Animals↗
PubMed1991

The skin tumorigenic and carcinogenic effects of different doses, numbers of dose fractions and concentrations of 7,12-dimethylbenz[a]anthracene in acetone applied on hairless mouse epidermis. Possible implications for human carcinogenesis.

Groups of hairless mice were painted with the carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) dissolved in reagent-grade acetone in various doses, dose fractions and concentrations. The animals were examined once a week for an appropriate time period and skin tumors were registered and classified as tumors (all tumors appearing) and as malignant tumors. The results show that dividing a particular dose of DMBA into an increasing number of applications was the factor that had the greatest tumorigenic and carcinogenic effect. This was found for total doses of 100, approximately 50 and approximately 26 micrograms DMBA. Similarly, increasing the size of the dose increased the effect on the tumor and carcinoma crop, but to a less pronounced event than splitting the dose into several fractions. The most striking of these effects was that a single dose of 51.2 micrograms DMBA gave a tumor rate of approximately 40%, whereas the same dose divided into 50 doses of 1 microgram gave a tumor rate of almost 100%. The final tumor yield increased from approximately 45 tumours per 32 animals after a single dose of 51.2 micrograms DMBA to approximately 250 tumors per 32 animals after 50 applications of 1 microgram DMBA. The final number of carcinomas per 32 animals was one carcinoma after a single application of 51.2 micrograms DMBA, and 40 carcinomas after 50 applications of 1 microgram DMBA. The paper includes a discussion on how these findings may be explained in terms of the complicated series of events that constitutes carcinogenesis. If it is biologically plausible to regard agents for which there is sufficient evidence for carcinogenicity in experimental animals as representing a carcinogenic risk to humans, then it may also be plausible and prudent to infer that the dose schedule that represents the highest tumorigenic hazard for mouse skin may generally also be the dose schedule that involves the highest risk for humans. Thus, repeated exposure to small doses may be the most hazardous situation. This is unfortunately the way many human beings are exposed to cigarette smoke, sunshine and carcinogens in food, water, air and at the work place. As shown in a previous paper, an increasing time interval between each dose may also increase the risk.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Urethan (ethyl carbamate) is an effective promoter of 7,12-dimethylbenz[a]anthracene-induced carcinogenesis in mouse skin two-stage experiments.

Groups of hairless mice were painted with urethan alone, with the complete carcinogen 7,12-dimethylbenz[a]anthracene (DMBA) alone, and with an initiating dose of DMBA followed by continual treatment with urethan or with the promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The animals were examined once a week for an appropriate time period. Malignant and non-malignant skin tumors were registered and classified. Lung adenomas and other internal tumors were also counted. The results show that all types of treatment produced skin tumors, some of which were malignant. When urethan was used lung adenomas also appeared, along with a few other tumors. The results show that a 10% solution of urethan in acetone is a significant promoter, showing synergistic increase of DMBA-induced skin tumors, but urethan is not as strong a promoter as 10 nmol TPA. Urethan is said to be the pure initiator of skin carcinogenesis. Previously the author has shown that urethan alone is a complete carcinogen and here it is shown that it is also a promoter. Hence, the current hypothesis of urethan as a pure initiator in skin carcinogenesis has been disproved.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

Subacute inhalation toxicity of mineral oils, C15-C20 alkylbenzenes, and polybutene in male rats.

Male Wistar rats were exposed to mist and vapor of two mineral oils, two C15-C20 alkylbenzenes, and one polybutene at aerosol concentrations of 70 mg.m-3 and 700 mg.m-3 for 2 weeks. Of oil mist particles, 82-97 wt% were respirable (less than 4.7 microns). High-level exposure to polybutene was lethal to three of four animals, due to pulmonary edema. Elevated numbers of pulmonary macrophages and increased macrophage vacuolization were observed after exposure to the polybutene, both mineral oils, and one alkylbenzene. The same alkylbenzene produced body weight loss. Deposition analysis was performed for one mineral oil. No oil was detected in brain tissue, while retroperitoneal fat tissue contained 541 (401-702) micrograms oil/g tissue, half of this still present after an exposure-free period of 2 weeks. It is concluded that inhalation of the polybutene and one of the mineral cable oils tested here produces toxic effects in lung.

Adipose Tissue↗
PubMed1990

The teaching of organ pathology in European undergraduate education programs in medicine.

The European Society of Pathology has established a working group on the undergraduate teaching of pathology. At the IX European Congress of Pathology in Hamburg 1982 some general problems and opportunities regarding the teaching of pathology for undergraduate students in Europe were dealt with. We undertook to formulate the educational objectives of pathology for undergraduates and outlined the subject content necessary to achieve these objectives, how much time is necessary to teach pathology, and when during the medical course the teaching should take place. The results were published as an article in Path Res Pract 178, 518-519, 1984. At the Xth European Congress in Athens 1985 we dealt with the teaching of general pathology in European undergraduate education program in medicine, and both subject content, time, place, pedagogics and the construction of a syllabus guide in general pathology were discussed and defined in detail. The results of this discussion were published in Path Res Pract 181, 365-369, 1986. In two symposia in Porto we concentrated on the teaching of organ pathology as a subject of its own, apart from general pathology. This will be continued at the next congress in Ljubljana September 1-6, 1991.

Education, Medical, Undergraduate↗
PubMed1990

Tumorigenesis and carcinogenesis studies of a number of insulation oils and fluids on hairless and SENCAR mice with special reference to skin tumours and malignant lymphomas.

Petroleum and synthetic hydrocarbons are used for the impregnation of paper-insulated power cables. To study the possible risk of skin cancer from such fluids a large series of hairless and a smaller series of SENCAR mice were exposed to long-term skin paintings with these fluids. The assayed fluids were two mineral oils, one C12-C20 polyisobutylene, two C14-20 alkylbenzenes, and one phenylxylylethane. The experiments were carried out according to three protocols: 1) A two-stage protocol using an initial single application of either 51.2 or 25.6 micrograms DMBA (7,12-dimethylbenz(alpha)anthracene) followed by long-term painting twice a week with 100 microliters of different concentrations of the fluids, with acetone as solvent; 2) a complete tumorigenesis protocol with long-term applications twice a week of the fluids alone or in various concentrations in acetone solution; and 3) a co-carcinogenesis protocol with long-term paintings with alternate applications twice a week of very small doses of DMBA and the fluid being studied. The animals were painted and/or observed for 18 months. Signs of skin toxicity, the occurrence of skin papillomas and carcinomas, swollen lymph nodes, and tumours and lesions in other organs found by autopsy were recorded. The results are documented in tables and in figures, and have been analysed by appropriate statistical methods. The oils were toxic to mouse skin, and had a certain general toxic effect indicated by a significantly increased death rate after long-term treatment with polyisobutylene, alkylbenzene A and PXE on hr/hr mice (see Appendix, p. 51), and there was also a tendency to increased amyloidosis. The fluids tested generally displayed a very low, non-significant tendency to induce skin tumours, mostly papillomas, and they are not significantly carcinogenic for skin. Generally, they do not enhance DMBA-induced tumorigenesis, with two exceptions (mixture of heavy mineral oils B/C after pretreatment with 25.6 micrograms, but not after 51.2 micrograms DMBA; and alkylbenzene A which very significantly enhanced DMBA-induced carcinogenesis, without enhancing tumorigenesis). Thus, in the concentrations used, the tested oils and fluids generally do not act as "promoters". On the contrary, most of them are so toxic that the number of tumours occurring after a single application of 51.2 micrograms DMBA is reduced by long-term applications of the oils and fluids, especially by higher concentrations, so in this respect they act in an antitumorigenic way. The fluids, except phenylxylylethane, were significant or suggestive inducers of malignant lymphomas in mice, either alone or in connection with initial treatment with DMBA.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenoma↗
PubMed1989

The influence of fixation on the relative amount of cytoplasmic ribosomes in mouse epidermal basal keratinocytes. A morphometric study of so-called "dark cells" and their putative role in epidermal carcinogenesis.

The nature and significance of so-called dark keratinocytes in the epidermis during chemical carcinogenesis is still a matter of concern and debate. Based on ultrastructural observations it has been suggested that dark cells most often are shrunken cells. Reports on skin carcinogenesis, however, claim that dark cells are a sign of ongoing tumor promotion and represent those stem cells in the epidermis from which the tumors originate. It is therefore important to find out whether these cells are simply injured and shrunken cells, or vital cells of great importance for carcinogenesis. Dark cells are assumed to be rich in ribosomes. There is evidence, however, that the observed number of dark cells is highly dependent on tissue fixation. In the present ultrastructural study, morphometric methods were used to compare the effects of two different fixation procedures on the amount of cytoplasmic ribosomes in dark cells from both untreated and carcinogen-treated hairless mouse epidermis. The results show that the ultrastructural features of both dark and clear cells vary considerably with different fixation procedures. In acetone-treated controls typical dark cells are only observed when the fixative has a lower osmotic activity than the plasma. With iso-osmolal fixation typical dark cells are not observed. After an abortive two-stage carcinogenesis treatment, in which a single application of 9,10-dimethyl-1,2-benzanthracene (DMBA) in acetone was followed by a single application of 12-O-tetradecanoyl-13-acetate (TPA) in acetone, signs of cell injury could be found after both fixation procedures. With DMBA/TPA and hypo-osmolal fixation the number of dark cells seemed to increase, whereas only signs of cell injury with occurrence of some heavily altered "clear cells" dominated the picture with iso-osmolal fixation. Morphometry showed that both the numerical and the volumetric densities of cytoplasmic ribosomes in basal keratinocytes varied most significantly with the fixation procedure used. The cytoplasmic volumes did not vary in a way that could explain these differences. One might therefore assume that the number of ribosomes depends on the fixative. Large swelling artifacts occurred when a fixative with low osmotic activity was used, leading to compression of neighboring cells. Hence, an increased ribosomal density reported previously in dark cells is probably related to such cell volume artifacts and does not reflect an actually increased quantity of ribosomes.(ABSTRACT TRUNCATED AT 400 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Enhancement of methylnitrosourea-induced skin tumorigenesis and carcinogenesis in hairless mice by pretreatment with a mitosis-inhibiting epidermal pentapeptide.

Two groups of 48 hr/hr mice (24 males, 24 females) were pretreated i.p. with 0.03 nmol of a synthetic epidermal mitosis-inhibiting pentapeptide (EPP), pGlu-Glu-Asp-Ser-GlyOH, dissolved in bovine serum albumin solution (BSA) at -6, -3 and 0 h before a topical skin application of 1 mg N-methyl-N-nitrosourea (MNU) in 100 microliters reagent-grade acetone. A control group was pretreated with three solvent injections only -6, -3 and 0 h before application. The results were also compared with a large, historical control group of 333 animals treated once with 1 mg MNU and without any pretreatment. The production of benign and malignant skin tumours was recorded and the results were assessed statistically. There was no statistically significant difference between the large control group without pretreatment and the actual control group pretreated with BSA. Pretreatment with EPP led to significant enhancement of the number of tumour-bearing animals with time and to a very significant increase in the total number of tumours. The group pretreated with EPP also developed more malignant skin tumours. The results are in agreement with earlier findings after i.p. pretreatment with crude skin extracts, hydroxyurea, or when MNU was applied in relation to diurnal rhythms in epidermal cell proliferation. They are also consistent with the assumption that EPP is one of the active growth-inhibitory substances in the epidermal extracts, and support the hypothesis that epidermal basal cells may be more sensitive to MNU-induced carcinogenesis when the rate of cell proliferation is low, because then more cells are in late G1 or early S phase where MNU binding to DNA may be relatively strong.

Animals↗
PubMed1989

Studies of the carcinogenesis and tumorigenesis of skin applications of dodecylbenzene on hairless mice.

Dodecylbenzene in various concentrations, dissolved in acetone to a final volume of 50 microliters, was applied twice a week for 78 weeks to the back skin of hairless mice, with or without pretreatment with 51.2 micrograms 9,10-dimethyl-1,2-benzanthracene (DMBA). A negative control group was painted with acetone only and a positive control group was given a single application of 51.2 micrograms DMBA. A few tumours developed but there was no significant skin tumorigenicity--that is, occurrence of benign or malignant tumours--by acetone alone, or by 16% dodecylbenzene. More tumours developed in the group treated with 80% dodecylbenzene than in the group treated with acetone alone or with 16% dodecylbenzene, but there was no significant difference between treatments with 16% and 80% dodecylbenzene. There was only a suggestive increase in tumorigenesis in the group given 51.2 micrograms DMBA and thereafter painted with 40% dodecylbenzene twice a week compared with the group given 51.2 micrograms DMBA once. As regards histologically malignant tumours--that is, carcinogenicity--the group treated twice a week with 16% dodecylbenzene alone developed two skin malignancies, whereas only one carcinoma was observed in the group treated with 80% dodecylbenzene; both results are non-significant. There was only a suggestive increase in the occurrence of skin malignancies in the group treated with DMBA followed by 40% dodecylbenzene compared with that treated with DMBA alone. As regards other tumours, treatment with 80% dodecylbenzene led to six lymphomas in 56 animals, whereas the acetone control group had two lymphomas in 56 animals, a difference which is only suggestive. DMBA alone and DMBA followed by dodecylbenzene gave five and four lymphomas, respectively. There was no significant difference between controls and dodecylbenzene painted animals for lung adenomas or other tumours. A pronounced epidermal hyperplasia, an increase in melanin pigment ("blue spots"), pigment leakage, and skin ulcerations were seen, mainly after 80% dodecylbenzene and after DMBA followed by 40% dodecylbenzene. There was no obvious increase in amyloidosis after continual treatment with 80% dodecylbenzen. The results indicate that 80% dodecylbenzene alone is weakly tumorigenic but not carcinogenic in the skin of hairless mice, and it tends slightly to enhance DMBA initiated tumorigenesis and carcinogenesis. Dodecylbenzene may be a weak inducer of malignant lymphomas. It is a fairly strong skin irritant and may increase amyloidosis.

9,10-Dimethyl-1,2-benzanthracene↗