DNA modification in carcinogen risk assessment in relation to diet: recent advances and some perspectives from a MAFF workshop

Food is one of the ultimate complex mixtures to which man is exposed and which cannot easily be dispensed with. Apart from certain well studied microcomponents for example, food pyrolysates, Sugimura 1990 human exposure to genotoxic agents arising from macrocomponents has been relatively little studied from the standpoint of DNA damage. The results of epidemiological studies into the relationship between diet and cancer have left many researchers with the impression that it is an intrinsically intractable problem which is perhaps best left well alone. However, given the popular conception that the normal human diet is safe and that such risks as there may be are due to contamination by pesticide and other chemical residues, there is clearly a need to evaluate the possible avenues open to investigators and which are likely to yield meaningful results which would enable scientifically based advice to be given to the public as to the best dietary habits. This overview of the current state of methodology for measurement of DNA damage in relation to diet as well as a summary of current MAFF supported work and future prospects in this area arose out of a workshop entitled DNA modification in carcinogen risk assessment held in London on November 18, 1996 . The object of this report is to summarize the results presented at the workshop and also to indicate the significance of the MAFF funded programme within the broader context of recently published studies from the international scientific community. Hence, a comprehensive review of all aspects of diet related DNA damage is beyond the scope of this article. The workshop was organized as part of the MAFF Risk Assessment Research Programme and contributes to an interdepartmental initiative, the Government Research Councils Initiative on Risk Assessment and Toxicology RATSC which aims to bring together regulators and toxicologists to discuss their respective perspectives on current problems in the risk assessment of chemicals. Further aims of RATSC are to identify subjects for future detailed workshops on specific issues and to identify priorities for research into toxic chemical risk assessment. The membership of RATSC is drawn from a wide range of Government Departments and Research Councils and is chaired by Dr David Shannon MAFF Chief Scientist .     

Exposure of humans to endogenous N-nitroso compounds: implications in cancer etiology

Two sensitive procedures to quantitate human exposure to endogenous N-nitroso compounds (NOC) and/or methylating agents have been developed. One, the NPRO test, is based on the excretion of N-nitrosoproline (NPRO) and other N-nitrosoamino acids in the urine, that are measured as an index of endogenous nitrosation, following ingestion of precursors. The NPRO test has been applied to human subjects in clinical and epidemiological studies, and the kinetics and dietary modifiers of endogenous nitrosation have been investigated. Results obtained after application of the NPRO test to subjects at high risk for cancers of the stomach, esophagus, oral cavity and urinary bladder are summarized. In most instances, higher exposures to endogenous NOC were found in high-risk subjects, but individual exposure was greatly affected by dietary modifiers or disease state. Vitamin C efficiently lowered the body burden of intragastrically formed NOC. In experimental animals 3-methyladenine (3-MeAde) is excreted in urine following exposure to methylating NOC. Humans normally excrete 3-MeAde, the origin of which remains unknown. Recently developed analytical methodology permits large numbers of human urine samples to be analyzed and a wide variation is observed. Preliminary results suggest a weak correlation between basal NPRO excretion and background 3-MeAde excretion. Taken together, the results point to an etiological role of endogenously formed NOC in certain human cancers, and provide an interpretation of epidemiological findings that have shown protective effects of fruits and vegetables against several malignancies.     

Sexual conflict,sex allocation and the genetic system

Decisions over what sex ratio to produce can have far-reaching evolutionary consequences, for both offspring and parents. However, the extent to which males and females come into evolutionary conflict over aspects of sex allocation depends on the genetic system: when genes are passed to the next generation unequally by the two sexes (as in haplodiploidy, for example), this biased transmission can facilitate a range of conflicts not seen in diploids. However, much less attention has been paid to these forms of sexual conflict, not least because it has not always been clear how the conflicts could be realized. Here we consider how biased gene transmission, as expressed in different genetic systems, enhances the opportunity for sex ratio conflict and give empirical examples that confirm that males and females have the opportunity to influence sex ratios.     

What,where and when: deconstructing memory

The ability of animals to remember the what, where and when of a unique past event is used as an animal equivalent to human episodic memory. We currently view episodic memory as reconstructive, with an event being remembered in the context in which it took place. Importantly, this means that the components of a what, where, when memory task should be dissociable (e.g. what would be remembered to a different degree than when). We tested this hypothesis by training hummingbirds to a memory task, where the location of a reward was specified according to colour (what), location (where), and order and time of day (when). Although hummingbirds remembered these three pieces of information together more often than expected, there was a hierarchy as to how they were remembered. When seemed to be the hardest to remember, while errors relating to what were more easily corrected. Furthermore, when appears to have been encoded as a combination of time of day and sequence information. As hummingbirds solved this task using reconstruction of different memory components (what, where and when), we suggest that similar deconstructive approaches may offer a useful way to compare episodic and episodic-like memories.     

Mating Behavior, Sexual Selection, and Copulatory Courtship in a Promiscuous Beetle

The function of male movements during copulation is unclear. These movements may be a result of the necessary mechanics of insemination, or they may also have further function, for instance, stimulating or courting a female during mating, perhaps influencing female mate choice. We present data from three experiments exploring the mating behavior and copulatory movements of the highly promiscuous beetle Psilothrix viridicoeruleus. Male mating success in the struggle over mating was not related to male or female size (measured by weight) but successful males were more vigorous in terms of copulatory movements. These males took longer to mount females but copulated longer and remained mounted longer. We discuss these results in terms of the mating system of Psilothrix and also in terms of observations of the timing of insemination during copulation. We suggest that copulatory movements in this species are best understood as copulatory courtship.