Avril D. Woodhead

Primary productivity and biogeochemical cycles in the sea

Honorary Lecture: Towards Understanding the Roles of Phytoplankton in Biogeochemical Cycles R.W. Eppley. Factors Limiting Primary Productivity in the Sea: Light: The Nature and Measurement of Light Environment in the Ocean J.T.O. Kirk. Factors Limiting Primary Productivity in the Sea: Nutrients: Nutrient Limitation and Marine Photosynthesis J. Cullen, et al. Estimation of Global Ocean Production: Satellite Ocean Color Observations of Global Biogeochemical Cycles M.R. Lewis. The Role of Marine Organisms in Primary Production: Phytoplankton Size S.W. Chisholm. New Production and Biogeochemical Cycles: The Importance and Measurement of New Production T. Platt, et al. Loss Processes and Material Recycling: Respiration R.J. Geider. Phytoplankton in the Global Context: Biosphere, Atmosphere, Ocean Interactions J.A. Berry. 17 additional articles. Index.

Temporal changes in the incidence of malignant melanoma: explanation from action spectra.

The incidence of malignant cutaneous melanoma has been increasing for more than 50 years, and is now rising more rapidly than that of any other cancer. This increase is not explicable by changes in the physical environment, particularly by any observed increase in UVB radiation (290-320 nm). The distribution of melanomas on the body differs from the site distribution of nonmelanoma skin cancer (relatively many more melanomas occur on areas of the body not chronically exposed to sunlight, such as the back of the trunk in males, and the legs in females). This localization of melanoma, together with its epidemiology, suggest that a change in lifestyle has contributed to the fast-rising incidence in many countries. There is no convenient mammalian animal model for malignant melanoma. However, certain inter- and intra-specific hybrids of fish of the genus Xiphophorus are very sensitive to light-induced melanomas; we have used them to determine the wavelengths effective in melanoma induction. The action spectrum has a relatively very large component in the UVA region (320-400 nm) compared to human erythema. Hence, if the human and fish spectra were similar, the use of sunscreens that minimize erythema would have little effect in preventing the induction of melanoma, and if people using sunscreens expose themselves to sunlight for longer periods, they will be increasing dramatically their exposure to these melanoma-inducing wavelengths. Such considerations are sufficient to explain the rising incidence of malignant melanoma and its distribution on the body.

DNA repair and longevity in three species of cold-blooded vertebrates ☆

Abstract The “error catastrophe” mechanism of ageing proposes that senescence results from the progressive accumulation of unrepaired damage to DNA throughout the life span. Studies of the changes in DNA repair capability in ageing cells both in vivo and in vitro have given ambiguous results, but a clear relation has been demonstrated in mammals between the DNA repair capacity and potential longevity. We have found no difference in excision repair capacity in cultured cells from three species of cold-blooded vertebrates, the long-lived turtle, with a potential life span of 118 + yr, the rainbow trout, 8 yr, and Amazon molly, with 3 yr.

Photoreactivation of pyrimidine dimers in DNA from thyroid cells of the teleost, Poecilia formosa.

Abstract— We have developed and used a simple technique to estimate the quantity of pyrimidine dimers in unlabeled cellular DNA. DNA is extracted from cells, treated with an endonuclease specific for dimers, and its molecular weight estimated by its electrophoretic mobility on alkaline agarose slab gels. The technique is used to show that cells from thyroid tissue of the fish Poecilia formosa have photoreactivating activity towards dimers in the cellular DNA.

Localization of a CDKN2 gene in linkage group V of Xiphophorus fishes defines it as a candidate for the DIFF tumor suppressor

The Xiphophorus hybrid melanoma model represents one of the earliest reported cases of genetically regulated tumor susceptibility. Melanoma formation in Xiphophorus hybrids may be explained by the inheritance of two genes: a sex‐linked oncogene, Xmrk, and a putative tumor suppressor locus, termed DIFF, located in Linkage Group V (LG V). Several genetic mapping procedures were used to produce a new Xiphophorus LG V map with 20 loci. All markers, particularly a recently cloned Xiphophorus CDKN2 gene family member, called CDKN2X, were tested for associations of genotype with degree of macromelanophore pigment pattern modification and susceptibility to melanoma formation in backcross hybrids of seven genetic types, involving 1,110 fish and three pigment patterns. Highly significant associations of CDKN2X genotypes with such phenotypic effects suggests that this gene is a strong candidate for the classically defined DIFF tumor suppressor gene. Because published results have documented the involvement of the CDKN2A (p16, MTS1, and INK4A) tumor suppressor gene in human melanoma formation, the possibility of CDKN2 genes acting as tumor suppressors in both man and Xiphophorus is likely. Genes Chromosomes Cancer 22:210–220, 1998.

NONMAMMALIAN MODELS FOR SUNLIGHT CARCINOGENESIS : GENETIC ANALYSIS OF MELANOMA FORMATION IN XIPHOPHORUS HYBRID FISH

Abstract— Genetic hybrids of Xiphophorus fishes have been used for decades to study heritable melanoma formation. In these models, overexpression of pigmentation patterns from melanin‐producing pigment cells can lead to genetically regulated melanoma formation in backcross hybrids. In the best studied of these models, the Gordon‐Kosswig hybrid melanoma, tumors form spontaneously in all individuals of a subset of backcross hybrids between the platyflsh Xiphophorus maculatus Jp 163 A and the swordtail species Xiphophorus helleri. Backcross hybrids susceptible to melanoma formation inherit a sex‐linked oncogene, Xmrk, associated with the spotted dorsal (Sd) pigment pattern and have lost both copies of an autosomal gene, DIFF, from the X. maculatus parent. Spontaneous melanoma formation conforms to simple, two‐gene Mendelian inheritance in which DIFF behaves as a recessive tumor suppressor gene. Recently, Xiphophorus hybrids in which melanomas can be induced by UV and near‐UV visible light exposure have been described. We report here results of genetic linkage analysis of one of these Xiphophorus light‐inducible hybrid melanoma models, in backcross hybrids between the two platyflsh species X. maculatus Jp 163 B and Xiphophorus couchianus. Our linkage results provide the first estimate of recombination between the tumor suppressor locus, DIFF, and glycerate‐2‐dehydrogenase (GLYDH) in Xiphophorus linkage group V. Also, they demonstrate that DIFF regulates hyperplasia of spotted side (Sp) pigment cells in this hybrid model, analogous to its regulation of hyperplasia of Sd pigment cells in the “classical” Gordon‐Kosswig hybrid. Joint segregation analyses of melanoma‐bearing fish indicate that segregation of DIFF is genetically linked to melanoma induction by 405 nm light in this model but that induction of melanomas by UV wavelengths apparently does not depend on segregation of the DIFF locus.

Clinical aspects of neutron capture therapy

This document contains 36 papers presented at a conference on the current states of boron neutron capture therapy. Topics include radiation dose rates, clinical trials, dose fractionation, therapeutic results, neoplasms, radiation tolerance, and the blood-brain barrier. Individual papers are indexed separately for the data base. (TEM)

Aging, The Fishy Side: An Appreciation of Alex Comfort’s Studies

Many years ago, Alex Comfort experimentally refuted Bidders hypothesis that fish potentially were immortal. Later morphological and physiological studies, together with observations from fish populations in the wild, revealed that fish age in a way similar to that in other vertebrates. More recently, assessments of the age of fish have been revised, and have shown that some species live much longer than was estimated. These findings, together with the difficulties of demonstrating any increase in the rate of mortality with age in the long-lived, heavily exploited populations of fish, revived Bidders ideas. I briefly review some of the more recent literature, and conclude that there is no evidence to suggest that fish are exceptional; like other vertebrates, sooner or later they grow old and die.

MNU Induction of Neoplasia in a Platyfish Model

Interspecific hybrid crosses between members of the fish genus Xiphophorus have been used for over 70 years to study the genetic aspects of melanoma formation. In the well-established “Gordon-Kosswig” cross, the platyfish X. maculatus is outcrossed to the swordtail X. helleri, and the resulting backcross segregants spontaneously develop melanoma. We recently produced a distinct cross between X. maculatus and another platyfish species, X. couchianus. X. maculatus strain Jp 163 A is homozygous for several X-linked pigment pattern genes, including the Spotted dorsal (Sd), Dorsal red (Dr), and Anal fin spot (Af). Af is a sex-limited trait, coding exclusively for melanophores distributed on the modified anal fin or “gonopodium” in the adult male fish. Within F1 and BC1 hybrids (to X. couchianus), the Sd pigment pattern is phenotypically suppressed, whereas Dr and Af are enhanced. We exposed BC1 hybrids to the direct-acting carcinogen N-methyl-N-nitrosourea (MNU). Treatment led to the development of schwannomas, fibrosarcomas, and retinoblastomas. In addition, numerous MNU-treated males that inherited Af developed a pronounced melanotic phenotype, with melanin-containing cells oftentimes totally covering the gonopodium and extending further to grow within the ventral regions of the fish. Genetic linkage analysis of the BC1 hybrids revealed a significant (p < 0.01) association between CDKN2X genotype and the phenotypic degree of melanization. Such an association is consistent with a locus within linkage group V playing a role in the development of melanosis and delineates three genetic preconditions and a carcinogenic scheme resulting in melanosis of the ventral regions of hybrid fish. The overall study further alludes to the potential of using Xiphophorus fish to study carcinogenic mechanisms for tumors other than melanoma (schwannoma, fibrosarcoma, and retinoblastoma) and should enable extensive pathologic and molecular genetic studies of derived neoplastic abnormalities.

Assessment of Risk from Low-Level Exposure to Radiation and Chemicals

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