As more data emerge, the significance of polyamine catabolism in polyamine homeostasis, drug response, and disease etiology is expanding. Importantly, the regulation and function of the polyamine catabolic pathway has emerged as a rational target for drug intervention in both chemotherapeutic and chemopreventive strategies. Mammalian intracellular polyamine catabolism had long been thought to be a two-step process primarily regulated by a rate-limiting acetyltransferase, spermidine/spermine N1-acetyltransferase (SSAT), followed by the activity of a constitutively expressed acetylpolyamine oxidase (PAO). However, as recent reports have clearly demonstrated, mammalian polyamine catabolism also includes the activity of a previously unrecognized spermine oxidase (SMO/PAOh1). The production of reactive oxygen species (ROS) and other toxic products by these various polyamine catabolic enzymes can result in both useful and potentially dangerous consequences. This chapter will examine some of the most recent findings related to polyamine catabolism and will address the cloning and characterization of mammalian polyamine oxidases, including the newly discovered SMO/PAOh1. Additionally, further characterization of the highly regulated SSAT, as facilitated by many recent advances with transgenic models, will be discussed with respect to the potential role that it and the oxidases play in determining response to various drugs and stimuli. Although the polyamine catabolic pathway is well described and being studied in multiple organisms, this work will focus primarily on results directly related to mammalian systems, with special emphasis given to the relationship between polyamine catabolism and human disease. Specifically, data indicating that the induction of polyamine catabolism by specific antitumor polyamine analogs plays a direct role in determining drug response will be discussed. Also to be examined is the recent recognition that the oxidation of polyamines contributes to disease processes, and the potential targeting of polyamine catabolism as a strategy for chemoprevention.

The oxidation of polyamines induced by antitumour polyamine analogues has been associated with tumour response to specific agents. The human spermine oxidase, SMO(PAOh1), is one enzyme that may play a direct role in the cellular response to the antitumour polyamine analogues. In the present study, the induction of SMO(PAOh1) enzyme activity by CPENSpm [N-1-ethyl-N-11(cyclopropyl)methyl-4,8,diazaundecane] is demonstrated to be a result of newly synthesized mRNA and protein. Inhibition of new RNA synthesis by actinomycin D inhibits both the appearance of SMO(PAOh1) mRNA and enzyme activity. Similarly, inhibition of newly synthesized protein with cycloheximide prevents analogue-induced enzyme activity. Half-life determinations indicate that stabilization of SMO(PAOh1) protein does not play a significant role in analogue-induced activity. However, half-life experiments using actinomycin D indicate that CPENSpm treatment not only increases mRNA expression, but also leads to a significant increase in mRNA half-life (17.1 and 8.8 h for CPENSpm-treated cells and control respectively). Using reporter constructs encompassing the SMO(PAOh1) promoter region, a 30-90% increase in transcription is observed after exposure to CPENSpm. The present results are consistent with the hypothesis that analogue-induced expression of SMO(PAOh1) is a result of increased transcription and stabilization of SMO(PAOh1) mRNA, leading to increased protein production and enzyme activity. These data indicate that the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA.

Many factors affect how people perceive the world and their environment, and how such perceptions affect lifestyle decisions, yet the relationship between personal perceptions about environmental hazards and diet is rarely examined. In this study, environmental concerns on a local and global scale were examined, along with dietary patterns, to determine if there were associations and age-related differences. The hypothesis that concerns about water pollution might be reflected in choices about seafood consumption was examined. Many aspects of dietary choices varied significantly by age, including (1) younger people ate more "fast food' than others, (2) subjects aged 22-32 yr ate more meals in restaurants than older or younger people, (3) older individuals drank more tea than younger subjects, while younger people drank more soda than older people, and (4) there were few significant differences in total fish and shellfish meals, although young people ate more meals of other types of meat. Individuals who rated their health the best reported significantly fewer seafood meals than others. People who listed pollution as the major environmental problem did not consume seafood less often than others. While pollution was listed as the most important environmental problem globally, people distinguished between air and water pollution only for Singapore. Although Singapore, with its rapidly expanding economy, has reason to be concerned about both water and air pollution, only 14% of those listing pollution as the main Singapore environmental problem mentioned 'water pollution." Singapore has been able to take measures to reduce water pollution from internal sources. Respondents considered air pollution a greater problem, perhaps reflecting recent haze disasters from deliberately set forest fires in Indonesia, which are beyond the direct control of Singapore or Singaporeans.

Understanding different patterns of fish consumption is an important component of the assessment of risk from contaminants in fish. While there have been extensive studies of fish consumption in Western cultures, less attention has been devoted to the role of fish and meat in the diets of people in other cultures. A survey of 212 people living in Singapore was conducted to examine the relative importance of fish, shellfish, and other meat in their diets and to ascertain whether there were differences as a function of age, income, education or gender. As expected, fish and shellfish played an important role in their daily diets. On average, people ate fish in about 10 meals a week, chicken for eight meals, and shrimp and pork for about six meals each. While nearly 8% never ate fish, 18% ate fish at all 21 meals a week and over 20% ate shellfish for all 21 meals. Income explained about 14% of the variation in the number of fish meals consumed, and age explained about 8% of the variation in number of chicken meals per week. There were no gender differences in the number of meals of each type. People less than 26 years old ate significantly more pork, chicken, and other meat meals and fewer shellfish meals than older people. People with higher incomes ate significantly more fish meals than those with lower incomes. Chinese individuals ate significantly more meals of pork, chicken, and other meat than other ethnic groups, and they ate only 26% of their meals at home, while others ate 33% of their meals at home. The data indicate a great deal of variation in the number of meals of fish, shellfish, and other meats eaten by the people interviewed, making dietary and risk assessments challenging.

The relationship between a history of substance use disorder and the early course of psychotic illness was examined in 96 subjects with schizophrenia and 106 subjects with affective psychosis followed in the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis. Subjects received a structured diagnostic interview and clinical ratings at baseline assessment and again 6 months later. The 6-month assessment included information about treatment received during the interval. A lifetime history of substance use disorder was associated with worse clinical functioning at 6 months for schizophrenia subjects, but not for those with affective psychosis. There were no significant associations of substance use disorder with type of treatment during the interval or with self-reported compliance with medication. Schizophrenia subjects were more likely than subjects with affective psychosis to report cannabis use during the interval and to meet criteria for cannabis use disorder.