Long-term Biological Consequences Research Articles

Adolescent alcohol and nicotine exposure alters the adult response to alcohol use.

Adolescence through young adulthood is a unique period of neuronal development and maturation. Numerous agents can alter this process, resulting in long-term neurological and biological consequences. In the clinical literature, it is frequently reported that adolescent alcohol consumption increases the propensity to develop addictions, including alcohol use disorder (AUD), during adulthood. A general limitation of both clinical and human pre-clinical adolescent alcohol research is the high rate of co-using/abusing more than one drug during adolescence, such as co-using/abusing alcohol with nicotine. A primary goal of basic research is elucidating neuroadaptations produced by adolescent alcohol exposure/consumption that promote alcohol and other drug self-administration in adulthood. The long-term goal is to develop pharmacotherapeutics for the prevention or amelioration of these neuroadaptations. This review will focus on studies that have examined the effects of adolescent alcohol and nicotine exposure on adult alcohol consumption, the hypersensitivity of the mesolimbic dopaminergic system, and enhanced responses not only to alcohol but also to nicotine during adulthood. Again, the long-term goal is to identify potential cholinergic agents to prevent or ameliorate the consequences of, peri-adolescent alcohol abuse.

BIOLOGICAL EFFECTS OF LOW-DOSE RADIATION FROM CT IMAGING.

The dramatic rise in diagnostic procedures, radioisotope-based scans and intervention procedures has created a very valid concern regarding the long-term biological consequences from exposure to low doses of ionizing radiation. Despite its unambiguous medical benefits, additional knowledge on the health outcome of its use is essential. This review summarizes the available information regarding the biological consequences of low-dose radiation (LDR) exposure in humans (e.g. cytogenetic changes, cancer risk and radiation-induced cataracts. However, LDR studies remain relatively new and thus an encompassing view of its biological effects and relevant mechanisms in the human body is still needed.

Contribution of transposable elements to transgenerational effects of chronic radioactive exposure of natural populations of Drosophila melanogaster living for a long time in the zone of the Chernobyl nuclear disaster

The accident at the Chernobyl Nuclear Power Plant (ChNPP) led to the negative impact of chronic radioactive contamination on populations of organisms associated with the transgenerational transmission of genome instability. When the destabilization of genome, different genetic damages occur, the accumulation of which leads to the formation of mutations, morphological anomalies, and mortality in the offspring. The mechanisms underlying the manifestation of transgenerational events in the offspring of irradiated parents are not well understood. In this study, for the first time, the features of the influence of transposable elements (TEs) on the long-term biological consequences of the ChNPP are considered. In this work, specimens of D. melanogaster obtained from natural populations in 2007 in the areas of the ChNPP with heterogeneous radioactive contamination were studied. The descendants from these populations were maintained in laboratory (inbred) conditions for 160 generations. A stable transgenerational transmission of dominant lethal mutations (DLMs) to the offspring of all studied populations was shown. The DLM frequencies strongly were correlated with the level of survival of offspring. The mean frequencies of recessive sex-linked lethal mutations varied at the level of spontaneous point mutations. The simultaneous presence of P, hobo and I elements indicates that the studied populations do not have a definite cytotype, their phenotypic status is unstable. The behavior of TEs in the genomes of offspring depends not only on parental exposure, but also on origin of population, distance to the ChNPP, and inbred conditions. The obtained results confirm the hypothesis that TEs are involved in transgenerational transmission and accumulation of mutations by the offspring of irradiated parents. The TEs pattern present in the Chernobyl genomes of D. melanogaster is a peculiar of epigenetic mechanism for the regulation of plasticity and adaptation of populations living for many generations under conditions of a technogenically caused radiation background.

Year-round genetic monitoring of mixed-stock fishery of Atlantic cod (Gadus morhua); implications for management

Abstract Mixed-stock fisheries pose a challenge for fisheries management recommendations and management, as mixed stocks can lead to unintentional over- or under-exploitation of stocks, with both short- and long-term biological and economic consequences. This study demonstrates practical application and implementation of year-round high-resolution genetic stock monitoring in management of mixed Atlantic cod (Gadus morhua) stocks in western Greenland. Using a panel of 96 high resolution gene-associated SNPs, we identified the stock of origin for four cod stocks in the two major inshore mixed-stock fisheries. Contribution of individual stocks was quantified to identify if fjord sections, times of year, and fish size, would allow a “clean fishery” with a minimal contribution of the depleted West Greenland Offshore (WGO) population. High level of mixing was identified with 50% of inshore catches originating from the inshore stock, 20% from the East Greenland/Iceland offshore stock, and 30% from the WGO stock. Although some spatiotemporal variation of stock proportions was identified, a practice allowing exclusively fishing a specific stock was not possible. Accordingly, we demonstrate the need to allocate catches at the biological stock level and show that application of high-resolution genetics is a reliable and necessary tool.

Generation of Neurosphere-Derived Organoid-Like-Aggregates (NEDAS) from Neural Stem Cells.

Neurosphere cultures have been used to propagate and study the intrinsic properties of neural stem cells (NSCs) for more than two decades but this method has many limitations. It is well known that neurospheres fuse in culture, but the long-term biological consequences of this phenomena are not well characterized. We leveraged the fusion behavior of human neurospheres to improve upon this technique with our Neurosphere-derived organoid-like aggregates (NEDAS) culture method, allowing the fusion of human NSCs at high density, which were maintained in orbital shaker conditions for 8-12 weeks without passing leading to the formation of 3D organoid-like aggregates without the use of Matrigel. NEDAS organoids proliferate and self-organize into neural rosettes, expressing PAX6 and SOX2 in ventricular zone (VZ)-like proliferative areas. Outside these rosettes, we identified corridors of migratory radial glial progenitors expressing Phospo-vimentin, CRYAB. In addition to DLX2, CXCR4 + progenitors. Further, we found immature neurons within cortical-like areas highly enriched for DCX and TUJ1, in addition to GABA+ and excitatory VGLUT1+ neurons. Here, we provide a protocol to generate NEDAS, additionally, we present a protocol for immunostaining of NEDAS organoids for confocal imaging. This protocol may be useful to dissect the self-organization and morphogenetic programs of populations of human NSCs offering an advantageous alternative to the conventional neurospheres method, generating more cell type diversity, within tissue-like aggregates over extended periods of time without dissociation or passing. NEDAS may be a complementary method to cerebral organoids protocols from IPSCs. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Preparation and expansion of cultures of human neural stem cells in reduced growth factor basement matrix Basic Protocol 2: Formation and fusion of neurospheres derived matrigel-free organoid-like aggregates (NEDAS) Basic Protocol 3: Harvest, cryosection, and imaging protocol for NEDAS.

Insights from Population Genomics to Enhance and Sustain Biological Control of Insect Pests.

Biological control—the use of organisms (e.g., nematodes, arthropods, bacteria, fungi, viruses) for the suppression of insect pest species—is a well-established, ecologically sound and economically profitable tactic for crop protection. This approach has served as a sustainable solution for many insect pest problems for over a century in North America. However, all pest management tactics have associated risks. Specifically, the ecological non-target effects of biological control have been examined in numerous systems. In contrast, the need to understand the short- and long-term evolutionary consequences of human-mediated manipulation of biological control organisms for importation, augmentation and conservation biological control has only recently been acknowledged. Particularly, population genomics presents exceptional opportunities to study adaptive evolution and invasiveness of pests and biological control organisms. Population genomics also provides insights into (1) long-term biological consequences of releases, (2) the ecological success and sustainability of this pest management tactic and (3) non-target effects on native species, populations and ecosystems. Recent advances in genomic sequencing technology and model-based statistical methods to analyze population-scale genomic data provide a much needed impetus for biological control programs to benefit by incorporating a consideration of evolutionary consequences. Here, we review current technology and methods in population genomics and their applications to biological control and include basic guidelines for biological control researchers for implementing genomic technology and statistical modeling.

Socio-Economic Differences in the Development of Six-Year-Old Children in Rural Areas of East Poland

The aim of this study is to evaluate socio-economic differences in physical, cognitive, and motor development among six-year-old children living in rural areas. The study encompassed 228 children, including 118 girls and 110 boys living in different rural settlements in the Świętokrzyskie Province in Poland, who were selected through a combination of nonprobability and random sampling. The study was carried out from April to June 2014. A questionnaire was used to collect information from the parents of the children concerning the parents’ education, number of children in the family, and the number of persons per room. Based on the concept of socio-economic status (SES), three levels of quality of life conditions of each family, i.e., high, average, and low, were distinguished. The study noted considerable differences in BMI, and especially the cognitive development of the children with respect to the socio-economic status of their family. It was observed that children from rural areas who live in bad socio-economic conditions are exposed to a wide range of negative factors affecting their health, which leads to lower educational results and negative long-term biological and psychosocial consequences. The chance for more rapid alignment of development deficits for those children would have been their earlier cover of school duty.

Acute exposure to a commercial formulation of Azoxystrobin alters antioxidant enzymes and elicit damage in the aquatic macrophyte Myriophyllum quitense.

Azoxystrobin is a strobilurin of growing concern in aquatic environments because it is the most sold fungicide worldwide, however, the information available about its effect on aquatic non-target organisms is scarce. The objective of the present study was to evaluate potential physiological, biochemical, and genetic effects at environmentally relevant (1-10μg/L) and elevated (100-500μg/L) concentrations in the aquatic macrophyte Myriophyllum quitense exposed to the commercial formulation AMISTAR®. Following an acute 24-h exposure, there were no effects of AMISTAR® on photosynthetic pigments at any of the concentrations evaluated. Glutathione-S-transferase activity was significantly elevated at 1 and 10μg/L AZX. Significant decrease of catalase and guaiacol peroxidase activities in plants exposed to 500μg/L, and to 100 and 500μg/L, respectively, and an increase in glycolate oxidase activity at 500μg/L was observed. DNA damage at 100 and 500μg/L was observed. These data indicate that although environmentally relevant levels of AMISTAR® did not result cytotoxic, this fungicide was genotoxic, affecting the physiological process of photorespiration and caused oxidative damage at high concentrations. In this sense, it is necessary to explore sub-lethal responses in non-target organisms because some effects could promote further potential long-term biological consequences in a context of repeated pulses of exposure.

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes.

Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3-8% of all pregnancies in the US are complicated by preeclampsia and another 5-7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring. Pub Med and Web of Science databases were searched using the terms "preeclampsia," "gestational hypertension," "imprinting genes," "imprinting dysregulation," and "epigenetic modification," in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism. The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development. Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants.

Activation of homologous recombination DNA repair in human skin fibroblasts continuously exposed to X-ray radiation.

Molecular and cellular responses to protracted ionizing radiation exposures are poorly understood. Using immunofluorescence microscopy, we studied the kinetics of DNA repair foci formation in normal human fibroblasts exposed to X-rays at a dose rate of 4.5 mGy/min for up to 6 h. We showed that both the number of γH2AX foci and their integral fluorescence intensity grew linearly with time of irradiation up to 2 h. A plateau was observed between 2 and 6 h of exposure, indicating a state of balance between formation and repair of DNA double-strand breaks. In contrast, the number and intensity of foci formed by homologous recombination protein RAD51 demonstrated a continuous increase during 6 h of irradiation. We further showed that the enhancement of the homologous recombination repair was not due to redistribution of cell cycle phases. Our results indicate that continuous irradiation of normal human cells triggers DNA repair responses that are different from those elicited after acute irradiation. The observed activation of the error-free homologous recombination DNA double-strand break repair pathway suggests compensatory adaptive mechanisms that may help alleviate long-term biological consequences and could potentially be utilized both in radiation protection and medical practices.

Distribution profile of gadolinium in gadolinium chelate-treated renally-impaired rats: Role of pharmaceutical formulation

While not acutely toxic, chronic hepatic effect of certain gadolinium chelates (GC), used as contrast agent for magnetic resonance imaging, might represent a risk in renally-impaired patients due to free gadolinium accumulation in the liver. To answer this question, this study investigated the consequences of the presence of small amounts of either a soluble gadolinium salt (“free” Gd) or low-stability chelating impurity in the pharmaceutical solution of gadoteric acid, a macrocyclic GC with high thermodynamic and kinetic stabilities, were investigated in renally-impaired rats. Renal failure was induced by adding 0.75% adenine in the diet for three weeks. The pharmaceutical and commercial solution of gadoteric acid was administered (5 daily intravenous injections of 2.5mmolGd/kg) either alone or after being spiked with either “free” gadolinium (i.e., 0.04% w/v) or low-stability impurity (i.e., 0.06 w/v). Another GC, gadodiamide (low thermodynamic and kinetic stabilities) was given as its commercial solution at a similar dose. Non-chelated gadolinium was tested at two doses (0.005 and 0.01mmolGd/kg) as acetate salt. Gadodiamide induced systemic toxicity (mortality, severe epidermal and dermal lesions) and substantial tissue Gd retention. The addition of very low amounts of “free”, non-chelated gadolinium or low thermodynamic stability impurity to the pharmaceutical solution of the thermodynamically stable GC gadoteric acid resulted in substantial capture of metal by the liver, similar to what was observed in “free” gadolinium salt-treated rats. Relaxometry studies strongly suggested the presence of free and soluble gadolinium in the liver. Electron microscopy examinations revealed the presence of free and insoluble gadolinium deposits in hepatocytes and Kupffer cells of rats treated with gadoteric acid solution spiked with low-stability impurity, free gadolinium and gadodiamide, but not in rats treated with the pharmaceutical solution of gadoteric acid. The presence of impurities in the GC pharmaceutical solution may have long-term biological consequences.

The toxicity, ways of exposure and effects of Cu nanoparticles and Cu bulk salts on different organisms

Nanotoxicology is projected as an emerging branch of toxicology to address the gaps in knowledge and adverse health effects likely to be caused by nanomaterials. This branch of nanotoxicology would make an important contribution to the development of a sustainable nanotechnology and covers the physicochemical factors, routes of exposure, biodistribution, molecular factors, genotoxicity and regulatory aspects. It is also involved in proposing reliable, healthy, and safe test protocols for nanomaterials in human and environmental risk assessment. Some nanoparticles such as copper is harmful to aquatic life, a small fraction of its nanoparticles can dissolve in water and produce toxic impacts on fish and other aquatic life. Copper nanoparticles are widely used as antimicrobial (antiviral, antibacterial, antifouling, antifungal), antibiotic treatment alternatives, nanocomposite coating, catalyst, lubricants, inks, for filtration of air and liquid. Fish are vulnerable to copper nanoparticles because it can induce gill injury and acute lethality. They are also emitted as particulates from smelters, metal foundries, and as pollutant from asphalt and rubber tires. Their long-term biological consequences on aquatic species are still unclear so it is pertinent to assess the toxicity of Cu nanoparticles and Cu salt in aquatic life. In view of these facts the following review article presents the toxicity, ways of exposure and effects of Cu nanoparticles on different organisms in vivo and vitro.

Homeostasis of phospholipids — The level of phosphatidylethanolamine tightly adapts to changes in ethanolamine plasmalogens

Ethanolamine plasmalogens constitute a group of ether glycerophospholipids that, due to their unique biophysical and biochemical properties, are essential components of mammalian cellular membranes. Their importance is emphasized by the consequences of defects in plasmalogen biosynthesis, which in humans cause the fatal disease rhizomelic chondrodysplasia punctata (RCDP). In the present lipidomic study, we used fibroblasts derived from RCDP patients, as well as brain tissue from plasmalogen-deficient mice, to examine the compensatory mechanisms of lipid homeostasis in response to plasmalogen deficiency. Our results show that phosphatidylethanolamine (PE), a diacyl glycerophospholipid, which like ethanolamine plasmalogens carries the head group ethanolamine, is the main player in the adaptation to plasmalogen insufficiency. PE levels were tightly adjusted to the amount of ethanolamine plasmalogens so that their combined levels were kept constant. Similarly, the total amount of polyunsaturated fatty acids (PUFAs) in ethanolamine phospholipids was maintained upon plasmalogen deficiency. However, we found an increased incorporation of arachidonic acid at the expense of docosahexaenoic acid in the PE fraction of plasmalogen-deficient tissues. These data show that under conditions of reduced plasmalogen levels, the amount of total ethanolamine phospholipids is precisely maintained by a rise in PE. At the same time, a shift in the ratio between ω-6 and ω-3 PUFAs occurs, which might have unfavorable, long-term biological consequences. Therefore, our findings are not only of interest for RCDP but may have more widespread implications also for other disease conditions, as for example Alzheimer's disease, that have been associated with a decline in plasmalogens.

Increased frequency of micronuclei in adults with a history of childhood sexual abuse: a discordant monozygotic twin study.

BackgroundChildhood sexual abuse (CSA) is a traumatic life event associated with an increased lifetime risk for psychopathology/morbidity. The long-term biological consequences of CSA-elicited stress on chromosomal stability in adults are unknown. The primary aim of this study was to determine if the rate of acquired chromosomal changes, measured using the cytokinesis-block micronucleus assay on stimulated peripheral blood lymphocytes, differs in adult female monozygotic twins discordant for CSA.MethodsMonozygotic twin pairs discordant for CSA were identified from a larger population-based sample of female adult twins for whom the experience of CSA was assessed by self-report (51 individuals including a reference sample). Micronuclei (MN) contain chromatin from structurally normal or abnormal chromosomes that are excluded from the daughter nuclei during cell division and serve as a biomarker to assess acquired chromosomal instability.ResultsFemale twins exposed to CSA exhibited a 1.63-fold average increase in their frequency of MN compared to their nonexposed genetically identical cotwins (Paired t-test, t 16 = 2.65, P = 0.017). No additional effects of familial factors were detected after controlling for the effect of CSA exposure. A significant interaction between CSA history and age was observed, suggesting that the biological effects of CSA on MN formation may be cumulative.ConclusionsThese data support a direct link between CSA exposure and MN formation measured in adults that is not attributable to genetic or environmental factors shared by siblings. Further research is warranted to understand the biological basis for the observed increase in acquired chromosomal findings in people exposed to CSA and to determine if acquired somatic chromosomal abnormalities/somatic clonal mosaicism might mediate the adult pathology associated with CSA.

Late-Season Seed Production in Arable Weed Communities: Management Implications

Late-season weed escapes are often ignored because they rarely cause crop yield penalty. Traditional weed management recommendations are based on the economic threshold (ET) approach, wherein management is required if the predicted current-season yield loss is greater than the cost of control interventions. While ET-based weed management can reduce current-season production costs and promote farmland biodiversity, it does not consider the long-term biological and economic consequences associated with late-season weed seed production. An important concern is that late-season weed seed production will replenish the soil seedbank, ensuring future weed problems. In the context of herbicide resistance evolution, allowing late-season weed seed production can be problematic because the probabilities of occurrence of resistant mutants rise with increases in seed production. A key component of herbicide resistance mitigation and management is preventing seed production and buildup of the soil seedbank. Late-season weed management efforts constitute additional expenses to growers, which cannot be recouped in that growing season, but any such investment must be weighed against the perceived long-term benefits. It appears that management of late-season weed escapes is valuable in a number of situations, and the degree to which management interventions should be employed can be case-specific. Adoption of economic optimum thresholds (EOTs), which can be established using bio-economic models, will be useful for making management decisions for late-season weed escapes. In systems vulnerable to herbicide resistance evolution, bio-economic resistance thresholds (BERTs) will be appropriate and bio-economic resistance models (BERMs) will be helpful for establishing such thresholds for specific production scenarios. Management considerations for late-season weed escapes are discussed, and knowledge gaps for future research are identified.

Cow milk consumption, insulin‐like growth factor‐I, and human biology: A life history approach

To assess the life history consequences of cow milk consumption at different stages in early life (prenatal to adolescence), especially with regard to linear growth and age at menarche and the role of insulin-like growth factor I (IGF-I) in mediating a relationship among milk, growth and development, and long-term biological outcomes. United States National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and review of existing literature. The literature tends to support milk's role in enhancing growth early in life (prior to age 5 years), but there is less support for this relationship during middle childhood. Milk has been associated with early menarche and with acceleration of linear growth in adolescence. NHANES data show a positive relationship between milk intake and linear growth in early childhood and adolescence, but not middle childhood, a period of relatively slow growth. IGF-I is a candidate bioactive molecule linking milk consumption to more rapid growth and development, although the mechanism by which it may exert such effects is unknown. Routine milk consumption is an evolutionarily novel dietary behavior that has the potential to alter human life history parameters, especially vis-à-vis linear growth, which in turn may have negative long-term biological consequences.

Hip artroplasty: A transient reason not to be pregnant

Metal implants corrode and release metal ions, cobalt and chromium, which, in turn, may cause systemic toxicity, mostly in the first few months from implantation of metal-on-metal hip arthroplasty. At the time of delivery, the placenta reduces the passage of cobalt and chromium ions released from metal-on-metal prosthesis. From a biomechanical view point, hip replacement should not be considered a contraindication for pregnancy or for spontaneous delivery, and does not seem to have any negative effects in terms of risk of dislocation, loosening, fracture, or revision surgery, neither negative effects on clinical and functional outcomes. The long-term biological consequences of exposure to Co–Cr particles and ions remain largely unknown.

Limited ecological connectivity of an arboreal marsupial across a forest/plantation landscape despite apparent resilience to fragmentation

Demographic and genetic replenishment of populations through the exchange of individuals is essential for their persistence. Habitat loss and fragmentation can reduce the permeability of landscapes, hinder dispersal and compromise the genetic integrity of populations over time. We examined ecological connectivity in an arboreal marsupial, the common ringtail possum (Pseudocheirus peregrinus) in fragmented forests of southeastern Australia. This species is potentially robust to fragmentation based on its presence in degraded landscapes and known use of plantations for foraging and nesting. Using 312 individuals screened at 15 microsatellites, we measured dispersal and gene flow across seven native Eucalyptus forest remnants surrounded by exotic Pinus radiata plantations and three sites within a large continuous forest. The permeability of the pine matrix to dispersing possums was significantly lower than that of the native forest. Small, isolated patches exhibited signatures of genetic drift, having lower heterozygosity and allelic richness than possums in large patches. Most (87%) possums were born in their sampled patch or dispersed only short distances into neighbouring remnants. The continuous forest was identified as an important source of immigrants only for proximate patches (within 2.5 km), thus emphasizing for the common ringtail possum and more specialized arboreal mammals the need to conserve large, proximate forest remnants. Our findings highlight the importance of using genetic tools to understand the long-term biological consequences of fragmentation for effective management.

25 years after the accident at the Chernobyl nuclear power plant: Radioecological lessons

The area affected by the Chernobyl accident has become a unique test site where long-term ecological and biological consequences of a drastic change in a range of environmental factors as well as trends and intensity of selection are studied in natural settings. The consequences of the Chernobyl accident for biota varied from an enhanced rate of mutagenesis to damage at the ecosystem level. The severity of radiation effects was strongly dependent on the dose received in the early period after the accident. The most exposed phytocenoses and soil animals’ communities exhibited dose dependent alterations in the species composition and reduction in biological diversity. These findings make a valuable contribution to scientific and public understanding of the environmental risks of ionizing radiation and to debates on the environmental costs, benefits and risks of nuclear energy.

An integrated and adaptive management model to address the long-term sustainability of tourist interactions with cetaceans

Rapid growth in demand for tourist interactions with cetaceans in the wild constitutes a challenge to management. Short-term animal behaviour changes can have long-term biological consequences for individual animals and populations. This paper reviews the whale-watching management context, describing the interplay of the macro (global), meso (national/regional) and micro-level (local/site specific) policy, planning and management settings. Here, an integrated and adaptive management model based largely upon the delineation and monitoring of limits of acceptable change (LAC) parameters is proposed to address current shortcomings in the long-term sustainable management of whale-watching activities. Although no integrated management framework currently exists, a comprehensive management approach must be developed and applied in the interests of the long-term sustainable management of tourist interactions with cetaceans in the wild. The proposed management model highlights the importance of integrating multiple stakeholder perspectives in a way that is both research-informed and adaptive. Beyond tourist interactions with cetaceans, this management framework could be applied to a wide range of wildlife management contexts.